Machine learning models have the potential to make biopharmaceutical process development faster and more efficient by, in theory, allowing scientists to predict the impact of changes to parameters ahead of time.

The problem, according to recent research, is that the high-fidelity process information required to train machine learning models is expensive to generate and, as a result, in short supply.

One potential solution would be to include low-fidelity data, which indicate general process trends, in training sets, says lead author Mohammad Golzarijalal, PhD, a research fellow at the University of Melbourne’s digital bioprocess hub.

“The basic idea is that abundant low-fidelity data teach the model the broad global trend of the process, while a smaller amount of high-fidelity data corrects and refines these trends, aligning surrogate model predictions more closely with the available ground truth.

“A model trained only on limited high-fidelity data can overfit and perform poorly outside the conditions it has already observed. By learning useful trends from lower-cost data, a multi-fidelity model can improve predictive accuracy and explore a wider process space without requiring the same number of expensive experiments,” he says.

More accurate models could improve predictions about cell growth, viability, metabolite concentrations, and product titer. They could also guide media optimization, feeding schedules, seeding density, and operating conditions.

“One example discussed in our review is a recent study, which was performed in our own group, that combined 20,000 simulated CHO fed-batch data points with experimental data from 65 bioreactor runs.

“The multi-fidelity Gaussian-process models predicted final monoclonal-antibody titer more accurately than a model trained only on the experimental data,” Golzarijalal says.

Low-fidelity data

Low-fidelity process data can be from previous production runs or from cultures grown in bioreactor configurations that differ from those in the process under development. Such data can also be generated using low-cost mechanistic or empirical models.

Drug firms already use low-fidelity data to an extent, although, as Golzarijalal points out, use is usually limited. For example, scientists routinely draw on previous experiments to define parameter ranges, develop design-of-experiments studies, and guide process optimization.

“There is an opportunity to use these data more systematically,” he says, adding, “Multi-fidelity algorithms provide a structured way to determine how much information should be transferred from historical or simulated data to a current problem.

“This can make past experience more useful for prediction and decision-making, rather than treating each new program largely in isolation,” Golzarijalal adds.

The post Adding Low-Fidelity Data to ML Training Sets Could Yield Better Process Models appeared first on GEN - Genetic Engineering and Biotechnology News.

Researchers led by Roger Hart, PhD, senior fellow, Big Data Project lead, National Institute for Innovation in Manufacturing Biopharmaceuticals, and senior researcher Kelvin Lee, PhD, professor, University of Delaware, make the case not only for leveraging big data in your own company, but standardizing and sharing key insights industry-wide…without compromising proprietary information.

That opinion is based on results from a big data model developed through the MELLODDY Consortium (Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, GSK, Janssen, Merck KGaA, Novartis, and Servier).

As Hart, Lee, and colleagues report in a recent paper, the consortium pooled decades of proprietary data—some 2.6 billion data points spanning more than 21 million molecules and more than 40 thousand assays in on-target and secondary pharmacodynamics and pharmacokinetics—using a secure computing platform to jointly train a predictive drug-activity model. That shared quantitative structure-activity relationship model used “the chemical structure of potential drug compounds to predict how they will function,” they note.

Results, they say, significantly outperformed those of any of the individual members. Detailing those results in a separate article, Wouter Heyndrickx, PhD, machine learning scientist from consortium lead Janssen Pharmaceuticals, reports benefits in “most of the classification or regression tasks,” writing that the model generally enhanced predictivity, sometimes substantially. Notably, the median Relative Improvement of Proximity to Perfection for conformal efficiency exceeded 12%, with one exceeding 20%.

Prepping to share

“Many organizations are already pursuing in-house solutions,” Lee tells GEN. “The benefits are the ability to tailor the solution to one’s specific situation. But by participating in larger-scale efforts, one can benefit from shared learnings and efforts to accelerate the digital transformation. Ecosystem-wide efforts can enable the entire industry to advance digital tools and benefits in ways that might not be apparent to individual organizations.”

Achieving such results takes a lot of data management preparation, the researchers admit. They must:

• Standardize ontologies, schemas, and holistic data integration and break down data silo enterprise-wide
• Enable predictive strategies to optimize processes, such as those supported by digital twins, in silico process design, and hybrid mechanistic/ AI models
• Develop secure, shared datasets that enable data to be pooled while protecting sensitive and proprietary data
• Ensure interoperability and real-time data connectivity among sensors from multiple vendors so they can communicate accurately and in real- or near-real time
• Industry guidance and buy-in, including regulatory clarity, workforce development, and shared business cases that lower adoption barriers

It is, in a word, challenging.

Redesigning legacy data infrastructure is expensive and time-consuming, and multivendor operability is a low priority for equipment developers, Hart says. There are additional barriers, too. Regulators have not yet determined how such models will be evaluated in data submissions. And, finally, workers with combined expertise in biomanufacturing and data science are scarce.

Yet, there are clear advantages to standardizing big data and using it to populate shared models.

“Many organizations face similar challenges and opportunities related to development and manufacturing,” Lee says. “Supporting an industry-wide set of solutions can accelerate the learnings of individual organizations, facilitate tech transfers…foster greater flexibility and interoperability, and support federated learning.”

As the team emphasizes, “Companies that do not adopt these capabilities are competitively disadvantaged from realizing the full benefits of their big data in the biopharmaceutical manufacturing marketplace.”

The post Big Data Opportunities in Biomanufacturing appeared first on GEN - Genetic Engineering and Biotechnology News.

“We’ve been focused on combining this mechanistic model with the data-driven AI model to create a hybridized model,” explains Dong-Yup Lee, PhD, professor and head of the Bioprocess Digital Twin Lab at Sungkyunkwan University.

According to Lee, their digital twin differs from a conventional simulator or standalone model because it’s continuously connected to a multi-sensory modeling system, which collects relevant data from the bioreactor in their lab. The team, he says, has developed mathematical models of mammalian Chinese Hamster Ovary (CHO) cells and uses them to make predictions about how the cells will behave under different bioreactor conditions.

However, he says, predictions from the mechanistic model alone do not always achieve the accuracy or adaptability required for real-time operation. As such, the team has incorporated data-driven AI as a complement to provide more adaptive control of the bioreactor.

“One of the limitations of AI is, if you have lots of data, it’s good for prediction, but it can’t explain why,” he says. “So, we use what is called explainable (XAI).”

XAI can provide information about what input conditions are most strongly affecting process outputs, he says, rather than just providing a prediction. This added interpretability can provide multiple options for improving and controlling bioprocess performance.

According to Lee, the biggest challenge for the team so far has been integrating the mechanistic model with XAI in a way that connects data collection, prediction, and forecasting directly with process control.

“We’re probably at 80% on [developing] the hybridized model,” he says. “The remaining 20% is working out how these models can be linked to and interact with the control system and our future robotics.”

Bringing these aspects together, he says, will be a key focus of the team’s future research, with the ultimate aim of moving beyond predictive digital twins toward increasingly autonomous process operation.

Lee is open to industry collaborations, particularly around digital twins, advanced bioprocess monitoring, and autonomous biomanufacturing.

The post Hybrid Digital Twins Developed for Future Autonomous Labs appeared first on GEN - Genetic Engineering and Biotechnology News.

The opportunity is particularly compelling in biologics manufacturing, where the authors call real-time monitoring of cell health a “critical bottleneck.” Conventional apoptosis measurements, including offline fluorescent staining and lactate dehydrogenase release assays, can be destructive and provide limited temporal resolution. Dielectrophoresis (DEP), which exploits how polarizable cells respond to nonuniform electric fields, offers another approach: tracking the changing electrical signature of cells without labeling or destroying them.

Chinese hamster ovary (CHO) cells, which the review calls the “industry workhorse,” provide a striking example. Studies using dual-frequency DEP cytometry followed CHO cells during nutrient-starvation-induced apoptosis and found two distinguishable electrical phases. First came membrane remodeling and a reduction in membrane capacitance. Then cytoplasmic conductivity dropped sharply as ionic homeostasis broke down. In one study, apoptotic populations began appearing between 24 and 36 hours, and cytoplasmic conductivity fell to approximately 0.05 siemens per meter (S/m) compared with about 0.45 S/m in viable cells. A follow-up similarly found membrane capacitance declining gradually before cytoplasmic conductivity plunged to 0.07 S/m in apoptotic cells by 52 hours. Together, the changes provide an electrical timeline of cell death rather than merely an endpoint measurement.

Speed could make those signatures especially valuable on the manufacturing floor. The commercially available 3DEP platform has been used to capture electrical signatures from populations of roughly 20,000 cells within seconds. According to the review, such measurements can reveal emerging apoptotic subpopulations “hours before traditional biochemical markers become detectable.” Earlier warning could allow operators to adjust a process or select a more favorable harvest time before culture performance deteriorates.

The next step might be turning those measurements into automated decisions. The review highlights a 2026 analysis integrating electrical impedance data with supervised machine learning; a tuned random-forest model achieved 90% predictive accuracy and was proposed as a label-free “traffic-light” system for batch monitoring. Combining rapid electrical measurements with computational analysis could ultimately support autonomous intervention and optimized harvesting.

That vision is not yet routine bioprocess control, but the technology is moving beyond specialized laboratory experiments. Commercial DEP platforms are already increasing accessibility, and the authors see continued integration with computational modeling and machine learning as a route toward real-time automated systems. For biomanufacturing, the electrical life of a cell may become another process signal—one capable of warning that a culture is changing before conventional assays catch up.

The post Electrical Signals Sharpen Bioprocess Control appeared first on GEN - Genetic Engineering and Biotechnology News.

The year’s prize recognized foundational discoveries that helped explain a chemical asymmetry observed in living organisms.  Small molecules like amino acids exist as two variants that are mirror images, yet living organisms contain only one of these images while the other is rarely found in nature. Kagan and Soai’s work provided the answer to the question of how homochirality can emerge. Their discoveries have enabled chemists to drive chemical reactions that lead to homochirality, and have been beneficial to scientists that design reactions used in manufacturing to develop new drugs, flavors, scents, and other materials. 

Their combined efforts “have provided a solution to a chemical mystery that is over a century old,” said Heiner Linke, PhD, chair of the Nobel Committee for Chemistry. “The chemical reactions they have developed are spectacular.”

How homochirality emerges is “probably the most fundamental question in life,” explained Peter Somfai, PhD, a professor of organic chemistry at Lund University and a member of the Nobel committee for Chemistry, in an interview. Scientists have long wondered how it happened billions of years ago. “Now we mimicked it in a lab today, not the way it happened four billion years ago, it’s important to stress, but we have for the first time mimicked it.”

The core scientific question

Though chiral molecules exist as non-identical mirror images with potential biological effects, life is homochiral and built exclusively from left-handed amino acids and right-handed sugars. And different enantiomers can have dramatically different properties. “Many molecules occur in two different versions, like my hands. They are one another’s mirror image. They look alike, but they’re not identical,” Linke said. 

When scientists began experimenting with chemical reactions that can form two mirrored molecules, they typically obtained equal proportions of both. But attempts to produce only one of the mirror images, in the context of pharmaceutical development, for example, proved challenging. Some of the earliest discoveries about chirality can be traced back to the mid-19^th century to Louis Pasteur and his efforts to investigate the behavior of tartaric acid. The field also owes some insights to the work of the chemist Willy Marckwald, who carried out the first successful asymmetric reaction in the early 1900s. He succeeded by using a chiral catalyst which boosted the formation of one mirror image over the other. 

In their respective laboratories, Kagan and Soai made their contributions to the question of how homochirality emerges spontaneously. In 1986, Kagan discovered a new way of manipulating chemical reactions that made it possible to create a larger quantity of one of the images than had previously been thought possible. 

At the time, he and other chemists were working to refine asymmetric reactions with an eye towards producing pure enantiomers. Building on the work done by Marckwald and others, as well as mathematical contributions from Charles Frank, PhD, a theoretical physicist at the University of Bristol, scientists typically used catalysts comprising a metal atom and a chiral substance. They typically used an enantiomer that was as pure as possible the catalyst assuming that combining two mirrored enantiomers would result in a product with equivalent proportions of mirror images. 

Kagan questioned this belief that mixing left- and right-handed catalysts would produce a linear relationship in product chirality, explained Somfai in his remarks during the announcement. “For a long time, it was believed that if we mix a left and right-handed catalyst, the proportion of an ancillary in the product would correlate linearly to that in the catalyst.”

Kagan’s question led him to test driving a reaction with different combinations of enantiomers in the catalyst. Ultimately, he realized that the relationship to the proportions of enantiomers in the product was not linear as previously thought. One form of the catalyst, the left-right catalyst, drove the chemical reaction in a different way than the two other forms of the catalyst — the right-right or left-left forms. This meant that he had found a way to enhance the formation of one enantiomer over the other. In 1986, he described at least three different asymmetric reactions that displayed what chemists call non-linear effects. 

Other scientists were keen to build on Kagan’s discovery, including Soai. While studying an asymmetrical chemical reaction with a non-linear effect, he discovered similarities between the structure of the reaction’s catalyst and the products. That discovery suggested that it may be possible to design a reaction in which the catalyst formed itself in an autocatalytic process. After experimenting with different molecules, Soai published a paper in 1995, where he described finding a chiral substance that could create itself although it did not achieve 100 percent enantiomeric purity. 

Eight years later, in 2003, he was finally able to present a chemical reaction, dubbed the Soai reaction,  in which only one of the two possible mirror images was formed. Specifically, the chemical reaction results in an excess of an enantiomer which then forms copies of itself, marking the first time a scientist successfully generated chirality from achiral or racemic conditions outside of nature.  As Somfai put it in his remarks “this is probably the coolest experiment in organic chemistry.”

Following the award announcement, Soai took questions from the press during which stated that he was out shopping near his home in Hiroshima, Japan when he got the call from the committee letting him know he and Kagan would share this year’s prize. “There are many excellent researchers in this field, so I’m very especially glad to receive this prize” and “to share the prize with Professor Henri Kagan, such a famous organic chemist,” he said. 

Basic research with a broad impact

Though this award recognizes basic organic chemistry research, Kagan and Soai’s work has been hugely impactful in both industrial and pharmaceutical manufacturing. Many active drug molecules are also chiral with only one compound having a desired therapeutic effect. The other might have no therapeutic effect or even be harmful. Given these risks, “we need methods to selectively prepare them, and in developing such methods, the findings of this year’s Nobel laureates are important. They provided powerful tools for this,” Somfai said.

The post Kagan, Soai Win 2026 Nobel Prize in Chemistry for Discoveries Related to Asymmetric Organic Synthesis appeared first on GEN - Genetic Engineering and Biotechnology News.

As genomic research tackles increasingly complex biological questions, researchers need tools capable of looking beyond the most readily resolved regions of the genome. Repetitive sequences, structural variation, and other complex genomic features can be challenging to resolve with many conventional sequencing workflows. At the same time, laboratories must balance accuracy and speed with practical considerations, including read length, throughput, batch size, and access to data.

Sequencing by expansion (SBX), the technology underlying Roche’s AXELIOS 1 platform, takes a different approach to these challenges by physically expanding the space between encoded bases before detection.

Creating space for a clearer signal

SBX leverages a specialized polymerase that converts the sequence of a target DNA or RNA molecule into a measurable surrogate polymer called an Xpandomer, using nucleotide analogs. The resulting Xpandomer is approximately 50 times longer than the original molecule, creating greater physical separation between encoded bases.

The Xpandomer is then measured as it passes through a reusable complementary metal-oxide semiconductor (CMOS) sensor containing millions of nanopores. Its high signal-to-noise reporters are designed to support accurate, ultra-rapid single-molecule sequencing with near real-time base calling and analysis. This architecture may help researchers investigate a range of genomic features, including single nucleotide variants, insertions and deletions, copy-number alterations, repetitive sequences and other complex structures.

Flexibility beyond chemistry

The utility of a sequencing technology depends on more than chemistry alone. Research needs can vary substantially from one project to another and even within the same laboratory. AXELIOS 1 pairs SBX chemistry with a sequencing architecture designed to accommodate that variability. The system offers configurable batch sizes, allowing researchers to run smaller batches without waiting to accumulate enough samples for a larger run.

Researchers can also adjust read length according to experimental needs, with reads up to approximately 1,500 base pairs (with a distribution from ~200bp to ~1500 bp) under appropriate sample and library preparation conditions. The platform is capable of end-to-end, same-day whole genome sequencing (WGS) in research workflows, while near real-time base calling and analysis enable access to data as a run progresses.

This flexibility extends across multiple research applications. SBX has been tested in proof-of-principle studies for WGS, RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), spatial analysis, and methylation studies. For each application, the AXELIOS 1 Platform sequences Xpandomer molecules that were created from libraries made with the AXELIOS 1 DNA Library Prep Kit. The data is then analyzed using the no-cost, open-source XOOS bioinformatics analysis suite tailored for SBX. Collaborations also support applications and tools across the sequencing ecosystem, including support for SBX through Google DeepVariant.

Broadening the genomic picture

Modern genomics rarely relies on a single experimental approach. Researchers may need to examine genomic variation, gene expression, cellular heterogeneity, or epigenetic changes to build a more complete biological picture. Sequencing platforms that accommodate different applications and project sizes can allow laboratories to design workflows around the scientific question rather than instrument constraints.

By combining a new approach to sequencing chemistry with flexible read lengths, batch sizes, and research applications, AXELIOS 1 is designed to expand the range of genomic questions researchers can pursue. As sequencing continues to evolve, these capabilities could help scientists interrogate previously challenging regions of the genome and build a more complete foundation for biological discovery.

For Research Use Only. Not for use in diagnostic procedures. AXELIOS is a trademark of Roche.

To learn more, visit go.roche.com/AXELIOS1article

The post Expanding the Possibilities of Next-Generation Sequencing appeared first on GEN - Genetic Engineering and Biotechnology News.

Panelists:

Erin Dieveney

Vice President, Quality Assurance
Aldevron

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Panelist

Erin Dieveney

Erin Dieveney leads quality assurance at Aldevron where she helps ensure the quality, compliance, and reliability of products that enable next-generation genomic medicines. Throughout her career, Erin has assumed increasing leadership responsibilities across quality, regulatory affairs, product development, and customer support, developing deep expertise in bringing innovative life sciences technologies to market.

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Khaled Yamout

Founder & CEO
Y-Chem Consulting

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Panelist

Khaled Yamout

Khaled Yamout is a thought leader in analytical sciences, quality and manufacturing. He was previously senior director of analytical services and quality control at TriLink Biotechnologies, where he oversaw the Analytical Sciences Center of Excellence and all analytical aspects of method development and validation to product release and stability, in support of regulatory filings for both small and large molecules. Prior to TriLink, Khaled held various positions in quality control, R&D, and manufacturing where he supported several drug products (small molecules and biologics) from clinical phase to commercial. His experience spans Fortune 500 firms as well as small entrepreneurial businesses in the areas of synthetic, analytical, colloidal, surface modification, protein, and antibody modification and purification.

Khaled holds a BS degree in chemistry from the University of Texas at Arlington.

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Kok-Seong Lim, PhD

Founder and Principal
Eight Crest Strategies

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Panelist

Kok-Seong Lim, PhD

Kok-Seong Lim, PhD, is a pharmaceutical leader with more than 20 years of experience in biological research and development, specializing in analytical sciences, quality control, and CMC strategy for advanced therapy platforms. He has held multiple management roles at Metagenomi, Aura Biosciences, Editas Medicine, and Thermo Fisher Scientific (formerly Brammer Bio), where he contributed to the advancement of more than ten gene therapies and CRISPR-based medicines for rare diseases and oncology indications.

Throughout his career, Kok-Seong has led the buildout of GMP-compliant facilities and analytical infrastructures to support early- and late-stage development. He has managed complex, multimillion-dollar budgets and contributed to regulatory submissions in both the U.S. and EU. Kok-Seong has served on committees such as the USP Biologics Expert Committee for Cell and Gene Therapy and the Standards Coordinating Body, helping to shape best practices and standards for the cell and gene therapy community.

Kok-Seong earned his PhD in biochemistry from the National University of Singapore and holds a BSc in pharmacy from the University of Strathclyde, Scotland.

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Michael Lehmicke

Senior Vice President, Scientific Affairs
Alliance for Regenerative Medicine

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Panelist

Michael Lehmicke

Michael Lehmicke joined the Alliance for Regenerative Medicine in 2019 as its first director of science and industry affairs. Michael has over 20 years of R&D experience in biomaterials, medical devices, and regenerative medicine. He has led product development teams for class II devices, human cell and tissue-based products, and drug/device combination products. He is a creator and an inventor with multiple U.S. patents to his name.

Michael has an MSc in biomedical engineering, with a focus on tissue engineering, from Drexel University. Michael’s areas of expertise include cell-based tissue engineering, bioceramics, biodegradable polymers, project management, strategic pipeline development, and business development.

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As biologics become more diverse, complex, and faster-moving, how can the biotech and biopharma industry ensure that quality standards keep pace with innovation? We will address this fundamental question in the latest GEN Spotlight on Biologics Standards for Innovation, Quality and Access, presented in partnership with USP. This virtual event will explore how evolving standards can provide a stronger foundation for developing and manufacturing next-generation therapeutics.

This Spotlight on Biologics Standards for Innovation, Quality and Access brings together experts from across biopharma, standards development, and analytical science to examine the challenges of testing increasingly complex modalities, including monoclonal antibodies, cell and gene therapies, and RNA therapeutics. Sessions will explore when and how to standardize emerging therapies, a practical layered framework for quality—from raw materials and analytical methods to identity, purity, and potency—and the growing importance of community input in developing standards for new modalities.

Session highlights include:

• A roundtable explores layered frameworks to ensure quality in multi-modal therapeutic development featuring Erin Dieveney (Aldevron) and Kok-Seong Lim, PhD (Eight Crest Strategies).
• A panel discussion on building standards for a multi-therapeutic modality future, featuring Khaled Yamout (Y-Chem Consulting) and Michael Lehmicke(Alliance for Regenerative Medicine)
• And a discussion featuring senior executives from USP on the importance of community input in developing standards for new modalities.

Join us on Wednesday, October 14, to discover how standardization can reduce development risk, support innovation, and help establish a shared foundation for the future of biologics.

Registration for this 2.5-hour event is free.

Produced with support from:

The post Biologics Standards for Innovation, Quality and Access appeared first on GEN - Genetic Engineering and Biotechnology News.

The drug, Aqneursa^® (levacetylleucine), was approved by the FDA in September 2024 for neurological manifestations of Niemann-Pick disease Type C (NPC) in adults and children weighing 15 kg (33 pounds) or more,  and by the European Medicines Agency (EMA) in January.

On September 18, the FDA approved a supplemental New Drug Application expanding the label of Aqneursa to become the first and to date only drug approved for the treatment of ataxia in ataxia-telangiectasia (A-T) patients weighing 15 kg (33 pounds) or more. Aqneursa is now under review by the EMA for adults and children diagnosed with A-T.

“The planned acquisition of IntraBio actively demonstrates Shionogi’s solid commitment to building a leading global rare disease business,” Isao Teshirogi, PhD, Shionogi’s president, CEO, and representative director said Monday in a statement. “Bringing Aqneursa to Shionogi after our acquisition of Radicava^® will deepen our commitment to rare disease communities, expand our capabilities and strengthen our portfolio as we advance future innovation for patients with significant unmet needs.”

Investors initially appeared less enthusiastic about the IntraBio acquisition, as Shionogi’s shares traded on the Tokyo Stock Exchange fell about 4.5% Monday, from ¥2,786 ($17.61) to ¥2,661 ($16.82)—but the stock bounced back Tuesday, all but recovering with a 3.8% gain that sent shares up to Y2,763 ($17.47).

However, Sumant Kulkarni, a senior analyst covering biotechnology with Canaccord Genuity, viewed the deal more positively.

“In summary, this transaction underscores our view that companies with approved products for rare indications, neuro or otherwise, present significant scarcity value for strategics and investors alike,” Kulkarni wrote Monday in a research note. “We are not entirely surprised by this development, but are encouraged by the upfront consideration.”

Kulkarni added: “In fact, we were surprised that IntraBio had remained independent for the time it did, but the timing makes sense given the recent approval for A-T, which adds another leg to its story.”

‘Plenty of financial firepower’

The acquisition of IntraBio comes two months after Teshirogi told Bloomberg News in an interview that Shionogi was “actively pursuing” at least three acquisition opportunities: “From a cash flow perspective, we’ve become a company with plenty of financial firepower. If a good opportunity comes along, there’s absolutely no reason for us to hesitate over any M&A.”

Teshirogi also said Shionogi was looking to expand its U.S. and European manufacturing capacity in order to diversify its production base beyond Japan and thus reduce geopolitical risk over the next decade.

To that end, Shionogi pursued and won a U.S. government contract in April to establish a Stateside drug product manufacturing site for its Fetroja^® cefiderocol), a cephalosporin antibacterial indicated to treat adults with complicated urinary tract infections (cUTI) including pyelonephritis; as well as hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP).

The contract—awarded through the Biomedical Advanced Research and Development Authority’s (BARDA) Project BioShield—was initially funded at $119 million with multiyear options for a total of up to $482 million.

Shionogi signaled its intent to focus on rare disease drugs in April when it agreed to acquire Radicava (edaravone), a small molecule treatment for amyotrophic lateral sclerosis (ALS), from Tanabe Pharma for $2.5 billion and a potential royalty on future sales. At the time, Shionogi said the deal would benefit it by adding approximately $700 million in annual global sales during the company’s current 2026 fiscal year, which began on April 1.

59% leap

That would represent a 59% leap from Shionogi’s entire FY 2025 earnings before interest taxes, depreciation, and amortization (EBITDA) of ¥187.72 billion ($1.187 billion), up 4.7% from ¥179.296 billion ($1.134 billion) in FY 2024.

Radicava generated ¥94.491 billion ($597.582 million) in the 2025 fiscal year that ended on March 31 of this year.

“Through this acquisition, the Company aims to strengthen its business foundation and enhance its corporate value over the medium to long term by maximizing the value of edaravone and expanding its provision of solutions in the rare disease area,” Shionogi explained in reporting fiscal Q1 (April-June) 2026 results in August.

Radicava is marketed under that name as an intravenous (IV) infusion, and as an oral suspension called Radicava ORS. The IV version was approved by the FDA in 2022 and the oral suspension version, two years later.

Based in Austin, TX, IntraBio was established in 2015 to discover, develop, and commercialize therapies for neurodegenerative diseases with high unmet medical need, by commercializing research generated by its scientific co-founders—Professors Grant Churchill, PhD, Antony Gallone, PhD, and Frances Platt, PhD, all of the University of Oxford; and Michael Strupp, MD, of the University of Munich.

Privately held IntraBio finished last year with a $35.8 million net loss on net sales of $67.867 million—all of it generated from sales of Aqneursa—according to data disclosed by Shionogi in its announcement of the acquisition.

Shionogi is expected to close on its acquisition of IntraBio during this quarter, subject to customary closing conditions.

The post Shionogi Grows Rare Disease Portfolio with $2B IntraBio Acquisition appeared first on GEN - Genetic Engineering and Biotechnology News.

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Panelists:

Kevin Lance, PhD

Director, Product Management
Unchained Labs

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Panelist

Kevin Lance, PhD

Kevin Lance covers the Stunner portfolio globally at Unchained Labs. His expertise includes biophysical characterization of proteins, ADCs, nucleic acids, viral vectors, and LNPs. Prior to Unchained Labs, his research experience covered the fields of sustained antibody delivery and nanotechnology. He earned his Ph.D. in Bioengineering from the joint UC Berkeley – UCSF Bioengineering Graduate Program.

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Oligonucleotide therapeutics, including ASOs, siRNAs, aptamers, and now antibody- and peptide-oligonucleotide conjugates (AOCs and POCs) are gaining momentum fast. But the chemical modifications and conjugations that make them work also make them harder to characterize than classic nucleic acids. Accurate quantification is the foundation of almost every assay and understanding how to arrive at the right concentration factor is the critical first step that echoes through every downstream decision.

This webinar follows oligo quantification from method development through conjugate characterization. We’ll cover what to consider when setting concentration factors and how UV-Vis extends to measuring conjugation ratio in AOCs and POCs.

We’ll also explore the boundaries of dynamic light scattering in oligo and nucleic acid formulation development. Oligos are flexible and sticky, which makes them hard to characterize by DLS. We’ll show what DLS can and can’t tell you across different lengths of nucleic acid constructs, up through mRNA.

Finally, we’ll look at viscosity data for oligonucleotides and nucleic acids to answer in-demand questions on high-concentration formulation and subcutaneous delivery.

Key learning objectives

• Understand the pieces that influence concentration factors for oligonucleotide quantification
• Extend UV-Vis quantification to AOC and POC characterization, including conjugation ratio
• Set realistic expectations for DLS in nucleotide and nucleic acid characterization
• Understand the relationships between viscosity, formulations, and nucleic acids

A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelist.

Produced with support from:

The post Lock Down the Critical Factors in Oligo and Oligo-Conjugate Characterization with Stunner and Honeybun appeared first on GEN - Genetic Engineering and Biotechnology News.

Published in Nature Biotechnology, the paper, “Deep Learning Perturbation Models Can Outperform Baselines on Calibrated Metrics,” introduces a positive-control baseline and a framework for testing whether commonly used metrics can distinguish meaningful model predictions from less informative ones.

Genetic perturbation models, a subset of AI virtual cells, predict how activating or inhibiting genes will alter a cell’s transcriptome. If reliable, these models could support scalable in silico screens for therapeutic targets. However, recent studies found that sophisticated deep learning systems often failed to outperform simple baselines, raising doubts about whether the models captured perturbation-specific biology.

The researchers argued that part of the problem lies in the benchmarks themselves. “The promise of in silico perturbation models, or ‘virtual cells,’ is that the same scaling laws will apply, and that providing them with ever-increasing quantities of biological data and compute will improve their prediction of real-world experimental results,” Brendan Swain, PhD, CSO and founder of Shift Bioscience, told GEN. “However, early benchmarks of virtual cell models revealed apparently poor performance, casting doubt on their potential.”

To assess this issue, the team developed an “interpolated duplicate” positive control that combines the average perturbation profile with an independent technical duplicate, weighting each gene by the strength of evidence that it was affected. They then introduced the dynamic range fraction, or DRF, which measures how effectively a metric separates this positive control from a negative control.

Across 14 genetic perturbation datasets and 18 evaluation metrics, commonly used measures such as mean squared error and control-referenced Pearson correlation were often poorly calibrated, particularly in datasets with weaker perturbations. The authors also added that, “In contrast, weighted and rank-based metrics—including WMSE, weighted R_Δ²​, and normalized inverse rank (NIR)—consistently exhibited higher calibration across datasets, reflecting their shared design principle of emphasizing perturbation-specific signal.”

Using the better-calibrated measures, the researchers benchmarked nine deep learning models on tasks involving unseen single-gene perturbations and unseen gene combinations. Earlier models, including scGPT and GEARS, often surpassed uninformative baselines once their predictions were evaluated with calibrated metrics. More recent systems, including PRESAGE and scLambda, showed stronger performance, although results varied by dataset and metric.

The analysis also highlighted the importance of dataset design. In Norman19, where the training data covered only 0.63% of possible gene combinations, a simple additive baseline remained difficult to beat. In Wessels23, which covered 10.3% of possible combinations, multiple models surpassed the additive baseline, indicating that deep learning models can outperform additivity when trained on broader portions of the combinatorial landscape.

“Our findings show that by using well-calibrated metrics and the right dataset, virtual cell models can generate biologically meaningful insights,” said Swain. “As a result, we can use them with greater confidence to identify promising new targets that are relevant to aging and disease. We are applying this framework directly in our target identification program, focusing on targets whose inhibition can support both rejuvenation and treatment of age-related disease, giving us a clearly defined route towards clinical development.”

Shift Bioscience, a Cambridge, U.K.–based biotechnology company, plans to apply the framework in large-scale in vitro and in silico screens for inhibition targets relevant to cellular rejuvenation and age-related disease, initially focusing on fibrosis. “Ultimately, we hope these tools will guide researchers as they develop better and better virtual cell models,” Swain told GEN.

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Drug giants Eli Lilly and Novo Nordisk say patients taking their drugs age less quickly, according to readouts from molecular “aging clocks.”

Such clocks assess a person’s biological age by looking at changes to DNA that accumulate with time, or, in newer versions, by tracking levels of key proteins.

Both companies found that overweight or diabetic patients taking the drugs, called GLP-1s, had reduced biological age compared to those taking a placebo, although the difference varied widely, depending on which type of clock was used, and what organ was tested. 

Overall, the difference was around “two to three years,” according to Nikolaj Roed, a global project leader at Novo, who says the company has been seeing “improved biological age in our patients across trials and across different tissues.” 

The findings add to wide speculation among scientists that GLP-1 drugs, as they are known, are acting on basic causes of aging and might be a true longevity treatment.

“Two years is a pretty strong effect, in my book,” says Steve Horvath, a professor at the University of California, Los Angeles, who’s credited with inventing aging clocks. Horvath says the emerging data could provide “evidence that these GLP-1 drugs are actually what is known as geroprotectors, medications that slow or possibly even reverse biologic aging.”

The companies shared their findings over the weekend during Aging Research & Drug Discovery, a conference devoted to seeking scientific remedies for old age. While that quest has not yet produced any clear-cut success, some scientists now think Novo’s drug semaglutide (sold under the names Ozempic and Wegovy) is coming close.

“In an unhealthy population, I do think it’s an anti-aging drug,” says Vadim Gladyshev, a Harvard biologist who assisted Novo with its molecular measurements. “But in a healthy population, no one knows.”

The drugs cause weight loss by stimulating a receptor, GLP-1, that tells your brain you’re not hungry. Yet real-world studies have shown much wider benefit. The drugs improve kidney function, reduce blood pressure, and even sharply cut the overall chance of death.

“If the question is,‘Can semaglutide reach several diseases relevant to health span and aging?’ we know we can say the answer is yes,” said Alejandro Aguayo-Orozco, a senior scientific director at Novo, the Danish drug giant, during the meeting.

The next question to answer, he said, is whether such effects are accompanied by changes to molecular measures of biological aging: “When you intervene with semaglutide, does it actually move the clocks in any direction? And the answer is yes.” 

The company found that, over time, the drugs cause a wide slowdown in aging clocks—as much as 4 years in the case of a clock that looks at heart proteins. “I think it’s pretty clear that the organ age is shifting,” said Aguayo-Orozco.

The studies are also a huge boost for the science of aging clocks. Although these measures reflect a person’s age, it’s been uncertain if they are useful as true biomarkers. Now clock makers have evidence  that their readouts show a drop in age when people take drugs with broad, well-demonstrated benefits.  

“The clock people have been pushing for a decade to get this kind of study done,” says Yuge Ji, a biologist who previously worked in the field and now runs a startup, Reflector Bio. “It’s huge for them.”

As part of its study, Novo took blood draws from 10,052 people, half on the drug and half on a placebo. Their blood, collected at the start of the study as well as months later, was then measured with “proteomic clocks,” which use levels of key proteins to predict a person’s age and risk of dying. 

Scientists at Eli Lilly performed similar research on their GLP-1 drug, tirzepatide, using so-called “epigenetic” clocks that assess age by counting accumulated changes to DNA. Lilly’s study was smaller, but also found that for the most part, molecular time moved more slowly for people on the drug.  

“All the clocks are telling a consistent story that we’re seeing a reduction in age,” Kevin Duffin, vice president for aging research at Lilly, said during the conference. “It’s not like we’re going to reverse age by 30 years or something, but it’s a significant reduction.”

The molecules have become the best selling drugs in the world,, with Lilly’s tirzepatide, sold as Mounjaro for diabetes and Zepbound for obesity, topping the list with more than $36 billion in revenue to the company last year. Novo’s semaglutide, also sold under more than one name, was a close second.

Alex Zhavoronkov, the founder of Insilico Medicine, and the organizer of the Boston meeting, says that extending lives by even one year across the world’s population would be equal to tens of millions of lifetimes.  

Last month Zhavoronkov showed that one of his company’s drugs, for a lung disease, also reversed the signals from aging clocks. That drug is experimental, but Zhavoronkov has sought to promote the idea that humanity is entering a new era of longevity medicines. He also disclosed during the event that he has been “microdosing” the available weight-loss drugs, even though he is not overweight.

“I am on tirzepatide and I am an equal-opportunity injector of semaglutide as well,” Zhavoronkov said.

It was part of an effort to directly raise the question of whether the first mass-market anti-aging remedy is already here.

“Do you think a reasonable person should start taking semaglutide?” he asked Aguayo-Orozco, the Novo scientist, in front of a crowded audience.

“I am not a physician. I cannot answer that question,” Aguayo-Orozco replied.

Several people cautioned that GLP-1 drugs do have side effects, including muscle loss. That is one reason they might not help most people, says Horvath, who says he isn’t ready to take the drugs himself, although he’s thought about it.

“Clearly, the drugs have many benefits in obese people, but I did not yet see sufficient evidence that they will benefit skinny people,” he said. “I guess we will have to wait.”

Answers could start to emerge in a year or two. This past January, a US agency, ARPA-H, put $38 million toward a study in Texas that will attempt to determine whether semaglutide has anti-aging effects in healthy people over 60. That research will look at changes in cognition, mobility, and acuity of the senses.

That project also seeks to help define a regulatory pathway for anti-aging drugs and to “build a new therapeutic industry” around longevity.

Messenger RNA (mRNA) is expanding from pandemic-scale vaccines toward a wider therapeutic portfolio. Recent Phase 3 success for an individualized neoantigen therapy from Moderna reinforces the clinical relevance of the lower-volume end of that spectrum, while COVID-19 established the opposite extreme. Clinical success is encouraging emerging and established developers to advance RNA medicines either through CDMOs or by building internal capacities. For increased development and production efficiency, CDMOs and drug developers need fast changeovers and flexibility across sequences and scales. All-ScaleFlow integrates RNA synthesis, purification, buffer exchange, and LNP formation to help democratize development.

A patented semi-continuous IVT core

RNA synthesis begins with fixed IVT unit volumes injected into Dillico’s patented, spiral-shaped semi-continuous reactor (Fig 1). The reactor is held in a temperature-controlled environment. Each unitary volume (UnV) advances by one loop periodically and the mature IVT crude UnV exits for optional enzymatic treatment and quenching. This design preserves defined batch reaction conditions without relying on progressively larger batch vessels.

Continuous purification and RNA-LNP formulation

As illustrated in the process flow diagram (Fig 2), All-ScaleFlow integrates alternating multi-column chromatography (dT Oligo resin or monolith) and multi-stage SPTFF for RNA purification, concentration, and buffer exchange. Surge tanks buffer cyclic chromatography eluate and maintain controlled flow into continuous purification SPTFF and LNP mixing. After encapsulation, a second multi-stage SPTFF step removes ethanol and performs final buffer exchange before in-line dilution or excipient addition and sterile filtration. By coordinating flow rates and interfaces, the platform maintains continuous production from IVT crude to formulated mRNA-LNP while minimizing intermediate holds.

Automated cleaning and sterilization onboard

To reduce supply chain risks and achieve long-term sustainability, an automated clean-in-place and sterilization-in-place (CIP/SIP) station is integrated on the system. It uses common cleanroom utilities to clean and sanitize the stainless-steel process path. This could save up to 450 kg of single-use plastic (~200 k$) for a large-scale batch IVT production.

Demonstrated across RNA sequence types

The synthesis approach has been successfully demonstrated with multiple mRNA and self-amplifying RNA (saRNA) sequences with length ranging from 400 bp to 12,000 bp. Working across different sequences is important for a platform intended to serve diverse vaccines and therapeutics.

The Process Simulator turns a sequence into a master recipe

Dillico’s Process Simulator embeds mechanistic process models built from an empirical knowledge base generated through experiments with mainstream, off-the-shelf process components. From product and process requirements, it calculates the global constraints needed to operate the continuous process as a coordinated system and identifies robust conditions that meet quality attributes and throughput targets. This reduces the physical experiments required during process development and supports right-first-time execution, avoiding costly trial-and-error with production materials and analytical testing. Thanks to the Process Simulator, users will be guided through a structured, step-by-step workflow that facilitates technology transfer and lowers the entry barrier for teams new to continuous processing. As part of the digital infrastructure, real process data are contextualized, making them data-lake-ready.

Explore All-ScaleFlowTM and request the Evidence Package

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Introduction

Prions are infectious proteins that cause neurodegenerative diseases in animals including bovine spongiform encephalopathy (cattle), Creutzfeldt-Jakob disease (humans), and chronic wasting disease (deer, elk and other cervids).¹ Prion diseases, also known as transmissible spongiform encephalopathies, result from misfolded proteins that accumulate primarily in the cells of the nervous system including the brains of infected animals. More widely, protein misfolding is linked to diverse neurological and non-neurological diseases and further research is needed in many areas due to the central importance of protein folding and aggregation in biology.

Prions propagate after regularly folded prion proteins (PrP^C) are converted into misfolded, aggregation-prone PrP^Sc proteins that build up and yield amyloids. These misfolded proteins and their aggregates damage nerve and other cells and, over time, lead to a decline in brain function and ultimately death.  With no cure available for prion diseases, researchers are striving to improve assay sensitivity and exploit the benefits of real-time monitoring to support the development of better diagnostic and treatment approaches.

RT-QuIC assays and microplate readers for prion analysis

Prions typically replicate by a series of sequential, amplifying events. Misfolded PrP^Sc acts as a point of recruitment of normal PrP^C cellular prion proteins. This interaction converts the recruited normal protein into the abnormal conformation setting in place a chain reaction where the protein-protein aggregates grow to produce a larger seed of misfolded proteins. As the aggregates grow, they can fragment to produce new nucleation sites. The seeds are eventually transformed into fibers of amyloid-rich assemblies that comprise significant amounts of beta-sheet conformations of the misfolded proteins.

The most widely used assay for detecting misfolded prions in biological samples is the RT-QuIC (Real-time quaking-induced conversion) assay. RT-QuIC assays are highly sensitive, seeding amplification assays that detect disease-associated prion activity. Formation of amyloid proteins is measured in real time using the fluorescent dye thioflavin T (ThT) whose emission increases significantly upon binding to beta-sheet-rich amyloid structures. Other dyes such as Congo Red are available that bind to amyloid but show reduced specificity for fibril proteins. Cyclic shaking accelerates fragmentation of the growing fibrils and produces a rapid amplification of the original prion seed. In practice, RT-QuIC assays generate characteristic amplification curves (figure 1) that comprise a baseline phase, an exponential increase in fluorescence, and a plateau phase. The lag time, maximum fluorescence, and reaction kinetics can provide quantitative or semi-quantitative measurements of prion seeding activity.

In the experiments shown in figure 1, scrapie brain homogenates were harvested 10 days after inoculation, incubated over time with shaking for the specified serial dilutions of Syrian hamster 263K cells, and ThT fluorescence was measured. The assays were quantified by measuring the loss of seeding activity at the end-point dilution.

Microplate readers and detection technologies for the investigation of amyloid

Microplate readers offer a robust platform for performing prion assays and measuring protein misfolding and aggregation. The ability to combine sensitive, high-performance kinetic fluorescence measurements with periodic cycles of rigorous shaking and consistent temperature control makes them the most widely adopted and practicable system for effective RT-QuIC assays.

Originally, the RT-QuIC assay was developed on the FLUOstar^® Omega microplate reader from BMG LABTECH which quickly became an international standard for prion analysis. BMG LABTECH readers, which continue to lead the way for prion detection and activity measurements, offer a robust platform for shaking for extended periods of time (over multiple days), while periodically reading the fluorescent signal as ThT is incorporated into amyloid aggregates.

Applications for protein misfolding

As mentioned earlier, protein misfolding has impact beyond prion disease and is a hallmark of impaired function in a wide range of conditions including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. The way certain proteins misfold and aggregate is closely tied to how proteins become toxic and cause neurodegenerative diseases.

BMG LABTECH´s application note “Monitoring amyloid-beta aggregation in real-time using a FLUOstar Omega microplate reader²” provides one example where the accumulation of misfolded amyloid protein aggregates linked to Alzheimer’s disease is measured using ThT. Figure 2 shows some signal curves for samples and controls where ThT incorporation into newly formed amyloid-beta fibrils is measured.

In figure 2, error bars represent the deviation of replicate wells within one plate from the mean. All signal curves show a clear increase in fluorescence with time. This increase illustrates the incorporation of ThT into the newly formed amyloid-beta fibrils. After some time, a plateau is reached that is considered as the endpoint of amyloid formation and ThT incorporation process.

Protein misfolding and aggregation are likely to play a critical role in many processes related to aging. Misfolded proteins are also thought to influence different aspects of metabolic dysfunction and amyloid accumulation although the mechanism for most of these effects remains poorly understood. ThT assays thus offer applications across multiple disease areas and research domains.

Future developments

RT-QuIC assays have significantly accelerated research and analysis into prions compared with earlier more costly and lengthy bioassays where infected animals were studied over months. RT-QuIC assays also offer potential for disease surveillance in populations of prion-infected animals in the wild that could impact public health. Researchers are also looking at ways to use RT-QuIC-based screening assays to ensure the safety of human food chains. In this context, microplate readers and RT-QuIC assays have been used in experimental settings to characterize prion-seeding activity in samples of tissue from wild and farmed deer that may have been exposed to chronic wasting disease.³

Beyond surveillance, new drugs are actively being sought for different targets related to protein folding and amyloid accumulation. In clinical trials, translatable biomarkers are needed that track the progression and severity of the neurodegenerative diseases impacted by protein misfolding and aggregation. Progress in artificial intelligence and modeling techniques will enhance studies of protein folding and misfolding which should bring further advances to the drug discovery space.

Demand for ThT assays is poised to increase due to the lack of interventions for neurological and non-neurological diseases caused by protein misfolding and aggregation events and the potential for other high-impact applications.

ThT-related assays are therefore moving away from being a means for a rapid diagnosis towards offering a quantitative tool for disease surveillance, pathogenesis, and therapeutic development across a wide range of disease and fundamental research areas in the life sciences.

BMG LABTECH offers a portfolio of single- to multimode microplate readers ideally suited for studying protein misfolding and aggregation. While the FLUOstar Omega remains the gold standard for RT-QuIC and seeding assays, the PHERAstar^® FSX was specifically conceived for screening campaigns and is the go-to reader for high-performance high-throughput screening. Both the VANTAstar^® and CLARIOstar^® Plus allow for wavelength flexibility and include Enhanced Dynamic Range technology for superior performance and ease of use. Collectively, these multimode readers combine high performance with miniaturized assays and short measurement times, delivering considerable savings on materials and other resources.

References

1. Dong TT, Satoh K. The Latest Research on RT-QuIC Assays-A Literature Review. Pathogens. 2021 Mar 5;10(3):305. doi: 10.3390/pathogens10030305.
2. Baumann F. Following Abeta Fibrillization/Aggregation in Real-Time | BMG Labtech. n.d. [Last accessed: 9/14/2026].
3. Li M et al. RT-QuIC detection of CWD prion seeding activity in white-tailed deer muscle tissues. Sci. Rep. 2021 Aug 18;11(1):16759. doi: 10.1038/s41598-021-96127-8. PMID: 34408204; PMCID: PMC8373970.l

If you are interested in further details about microplate-based evaluation of prions and protein misfolding, please contact us at applications@bmglabtech.com or scan the QR code on the right-hand side

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Today, despite the astounding breakthroughs of the past quarter-century, positive responses to advanced therapies such as checkpoint inhibitors and cell and gene therapies are still limited to a relatively small subset of patients. To improve efficacy and understand patient response, Stengel says, “We need to consider all layers of epigenetic regulation to better understand gene regulation and build better models of biology, especially right now, with AI enabling the integration of huge amounts of data.”

Despite the increasing influx of information, “We still have gaps in our understanding of how information flows from DNA to proteins and ultimately phenotype,” Stengel says. In a multiomics environment, RNA modifications—which she calls “an essential layer of that multiomic stack”—have received relatively little attention because they are considered particularly hard to measure accurately.

To help resolve that issue, AlidaBio is focusing on three of the most important RNA modifications as a way to create better and more useful epitranscriptomics models to improve scientists’ understanding of the many layers of epigenetic regulation.

Why epitranscriptomics

“Epitranscriptomics are a readout of the cell state,” Stengel says. “Single-cell transcriptomics and spatial transcriptomics have shown a huge amount of heterogeneity—similar cell types are characterized by different RNA expression patterns that define what a cell is doing at a given time.” As an example of the timescales of response, she says, “To reset DNA methylation can take up to two weeks. To reset an RNA expression pattern can take a day, and RNA modifications can change RNA expression within a few hours.” Understanding those patterns and their time to action can significantly affect a cell’s response to therapeutics.

“RNA modifications don’t change the genetic code, but they change what RNA does,” Stengel emphasizes. “N6-methyladenosine (m6A), the most important mRNA modification, can quickly mark RNA transcripts associated with a previous cell state for degradation and, at the same time, promote the translation of genes that are associated with the future cell state. It is also involved in alternative splicing regulation, which creates more protein diversity.”

Epitranscriptomics method development has gained significant momentum in recent years. Current nanopore-based direct RNA sequencing can detect a subset of modifications in native, long RNA molecules. However, the approach currently requires relatively large quantities of high-quality full-length RNA.

Short-read, one-pot detection

Alida Biosciences expanded the industry’s capabilities in 2025 by launching its EpiPlex platform. It was the first commercial solution to analyze sparse and highly-degraded RNA often found in clinical samples and provide simultaneous, one-pot detection, localization, and quantification of three of the best-studied and most frequently occurring mRNA modifications: N6-methyladenosine (m6A), inosine, and pseudouridine, along with gene expression. The company offers kits, analysis software, and services.

“To develop clinical and translational applications, you need to look at clinical samples (fresh-frozen or formalin-fixed paraffin-embedded tissues, and liquid biopsies, for example) that are present at low quantities or that may be highly degraded,” she explains.

The long list of potential applications includes patient stratification for specific therapies and response monitoring, as well as therapeutic development of cancer drugs and measuring immune cell fitness. “m6A, the most common modification, plays a huge role in cell differentiation and cell fate,” Stengel says.

Entrepreneurial leanings

Stengel formed the company five years ago, leaving a safe corporate position on the belief that she could create a company that would fill a key knowledge gap.

“I had spent a significant number of years in large companies—including Illumina—developing genomics technologies,” she says. Researchers at such companies, however, tend to be involved in either the inception or the development of a product. “I wanted to see things through from the beginning to the end. I thought a smaller company would be the ideal environment to do exactly that. I resigned my job and started putting the pieces together.

“When I started the company, many [in the industry] had never heard of epitranscriptomics,” she says. Nonetheless, she secured venture capital funding within six months and built a small, core team.

Those early days found her in the lab, working with just a few scientists. “Getting the first, preliminary data was so exhilarating!” she recalls. “It’s a good day when everything works in the lab.”

Epitranscriptomics is emerging from a niche discipline, so now most conference attendees, “regardless of the conference,” Stengel adds, are aware of the field. Although, she admits, “not everybody knows why they are important. Yet, that’s a huge step forward.”

Commercial vision

As scientists increasingly recognize the role RNA modifications play in therapeutic development and outcomes, she can focus on scaling the company and its commercial capabilities. “We started out very R&D heavy,” and now are beginning to earn revenue to fund further innovations. Potential clients include multiomics companies, research hospitals, and “to some extent, diagnostics,” she says.

Currently, AlidaBio is working with the oncology company STORM Therapeutics to understand the mechanism of action and to stratify patients for a Phase II drug that acts on methyltransferase-like 3 (Mettl3), the m6A writer enzyme. This is one of a few areas in which RNA modification can make breakthroughs in patient treatment and stratification, she says. “We’re also very interested in predicting response to PD-L1 inhibitors.”

For AlidaBio, bioinformatics is an area of continual focus, along with making analysis output more interactive. “We also are applying machine learning models to integrate the amount of information between RNA modifications and gene expression, so there will be significant updates to the EpiScout^® analysis software,” Stengel says. Other plans remain confidential.

For both the company and the industry, “I think the next inflection point is when epitranscriptomics becomes part of mainstream multiomics,” Stengel says. When that happens, researchers will consider RNA expression data incomplete without information about RNA modification.

Therefore, eventually, “RNA modifications will become another standard layer that’s integrated into AI models of biology,” she continues. “The real test will be demonstrating that this layer improves patient stratification, predicts treatment response, or identifies new therapeutic opportunities. Once that happens, I think the field will move from being scientifically interesting to clinically indispensable.”

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According to the company, the funds will support the development of what it claims is a first-of-its-kind platform for naturally modified mRNA medicines. The so-called Versatile Engine for Cell-based Therapeutic Optimization of RNA (VECTOR) platform integrates computational and artificial intelligence-enabled sequence optimization, high-throughput screening, and proprietary engineered eukaryotic cells to design and manufacture mRNA. Meanwhile, the company’s PromPT technology is designed to capture and protect mRNA inside cells before it is purified for therapeutic use. 

Specifically, Sensible will use the funds to expand VECTOR’s AI-enabled mRNA design and automated high-throughput screening capabilities as well as support the development of clinical-grade manufacturing capabilities. Sensible’s platform harnesses the natural machinery of living cells to produce naturally modified mRNA with reduced immunogenicity and high protein expression while avoiding double-stranded RNA contamination. Furthermore, by using engineered living cells, Sensible reduces reliance on specialized raw materials and manufacturing inputs, enabling more scalable production and expanding mRNA into therapeutic applications that require higher or repeated dosing.

Rather than relying on synthetic manufacturing technology developed more than 40 years ago, “we are taking a fundamentally different approach, using living cells to produce naturally modified mRNA while reducing the cost and supply-chain constraints of conventional production,” said Miroslav Gasparek, Sensible’s co-founder and CEO. “With this financing, we can scale our platform and expand mRNA into therapeutic applications requiring high or repeated dosing that have historically been limited by cost.”

The Series A includes participation from new investors OTB Ventures and In-Q-Tel, alongside existing investors Recode Ventures, Isomer Capital, Y Combinator, Backed VC, Kaya VC, Civilization Ventures, and BlueYard Capital, as well as the family office of Christoph Huber, co-founder of BioNTech, and Tim Garnett, former chief medical officer of Eli Lilly, and other individual investors.

In connection with the financing, Vishal Gulati, MD, FMedSci, managing partner at Recode Ventures, and Joel Schoppig, partner at Oxford Science Enterprises, will join Sensible’s board of directors alongside Miroslav Gasparek and Marian Kupculak, PhD, CSO and co-founder.

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Joe and Courtney Dion came to Washington to share their story: Peter, age 10, and Maggie, age 6, were born with limb-girdle muscular dystrophy (LGMD-R5, formerly known as LGMD-2C), a rare disease that would eventually rob the children of their ability to walk, move independently, and breathe on their own. 

At the time, there was little hope on the horizon.

“Our first conversation with the Dions was incredibly powerful—it became clear that they had done their homework. They identified a company with a promising gene therapy, but which could not progress to the clinic without significant investment,” explains Michele Oshman, BIO’s Chief Patient Advocate. “They also understood that investment could very well depend on the reauthorization of a little-known, but incredibly powerful federal program called the pediatric priority review voucher (PPRV). … For the cynics out there who think that maybe patient advocacy is not truly organic, they are wrong. It really is.”

From that day, the Dions made it their mission to get the PPRV reauthorized in time for Peter and Maggie to benefit from gene therapy. 

Oshman, along with Maggie, mom Courtney, and dad Joe Dion, was a keynote speaker at the Rare Trials Summit, held in Boston in September. The summit’s aim is to act as a working meeting for those responsible for advancing rare disease clinical programs. 

Oshman and the Dion’s conversation was a perfect example of just how effective patient advocacy can be when patients, innovators, and Congress work together toward solutions.  

What is the PPRV and how does it help patients?

Developing medicines for rare childhood illnesses is very expensive and risky because the market favors medicines that will be used in larger populations. 

Enter the Rare Pediatric Priority Review Voucher program. If a company develops and achieves FDA approval for a rare pediatric disease medicine, the FDA gives them a “voucher”. This voucher acts like a fast-pass ticket. The company can use it to buy time in the form of a 6-month FDA review instead of the standard 10-month review for their next innovation. The voucher is also an extremely high value asset that can be sold to another pharmaceutical company, thus enabling the rare disease innovator to invest tens of millions of dollars back into their R&D efforts.

The program is something many small, rare-disease-focused companies use to fund their current and future work, and has been a game changer for rare disease patients.

“Our children Maggie and Peter were diagnosed with limb-girdle muscular dystrophy in 2022,” explained Joe Dion. “At first, we didn’t know what to do. There was no cure. There were no trials. But there was one company that was potentially going to start a trial; it was a waiting game.”

But not content to just sit and wait, the Dion family got to work. 

“We started advocating and, fast forward to 2025, we got the first ever trial started,” he continued. “At the time, the PPRV program was something that made sense because this is an ultra rare disease. There weren’t enough patients to make it lucrative for investors to come in and invest in the typical pathway to get a drug developed. So the PPRV program was a big, big part of what helped us move things forward.”

In addition to advocacy, the Dions also hit the fundraising trail to supplement the research and development of treatment—including Joe being on Harpoon Hunters, a Discovery Channel reality TV show, to raise awareness. But an interesting thing to note about the Dion’s story is that their advocacy played a major role in bringing research into the United States.

The company that the Dions were working with was originally based in France and had already compiled pre-clinical data as a foundation for their work. It was the PPRV program that incentivized them to bring their business stateside and break the technology in the American market first. 

“The PPRV program was clutch in getting it to move forward,” said Joe.

Today, the company is still working to get their treatment to market and the Dions are continuing to ring the bell every step of the way. 

Navigating treatment—and recovery

“When we had the chance to be able to get our children treated with gene therapy, we put everything else on hold,” explained Courtney Dion. “We would have moved mountains. We would have gone to France. We would have gone to a third-world country if we had to. We would have sold our house. We would have done anything that we could have to have this opportunity.”

Luckily, the Dions only had to move to Florida for a short time.

And so the family moved and worked directly with the team down in Florida to navigate the clinical trial process, as well as see how it affected Maggie and Peter differently. For example, Maggie, who was able to get the treatment at a younger age, had a 92% expression in her recovery—an unprecedentedly successful amount—indicating the importance of getting these treatments out into the world faster and to patients earlier.

As Oshman pointed out, however, the Dions are in the game for the long run because there are more trials that need to be done, and more children that need to be helped. “These trials aren’t getting stalled because the medicine’s not working,” she reminded. “But because of the financing.” As such, the Dions have prioritized their fundraising efforts so that more children just like theirs can get access to these trials. 

Additionally, because of the work the Dions and advocates like them are doing, the PPRV program was reauthorized in February of 2026—ensuring that doors were opening for rare disease clinical research and development, not closing.

The power of the patient voice

The Dion’s experience is reflective of the power of patient advocacy: patient voices change the world, and their stories can put a human face on complex policy issues.

Another patient advocate at the event, Effie Parks, host of the Once Upon a Gene Podcast and mother to her son Ford, who was diagnosed with CTNNB1 syndrome, opened the event by saying, “When a trial becomes a possibility, we bring our children, our hope, our questions, and our trust. We can want progress with everything we have and still be frightened by what comes next.”

As Maggie Dion explained, “I love fighting for kids who don’t get a chance to go up and talk.” Not every child has the opportunity to speak as she does, she said; it is not a responsibility she takes lightly. 

The post In Rare Trials Summit keynote, BIO expert highlights lives touched by PPRV appeared first on Bio.News.

Deisseroth is a Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University and an HHMI Investigator; Hegemann is the Hertie Senior Research Chair for Neurosciences and a professor of Experimental Biophysics at Humboldt University and Nagel is a professor at the Department for Neurophysiology at the University of Würzburg, in Germany.

“Optogenetics provides opportunities for mapping the brain in a way that we could once only dream of,” says Per Svenningsson, MD, PhD, Chair of the Nobel Committee for Physiology or Medicine.

Although optogenetics is a relatively new technology, the seminal paper from the Deisseroth lab was published in 2005. However, the concept of manipulating specific neuronal cell types within intact circuits on a millisecond timescale was considered long before. Indeed, Francis Crick, PhD, once proposed a method where “all neurons of just one type could be activated or inactivated, leaving the others more or less unaltered.” He speculated that to “turn the firing of one or more types of neurons on and off in the alert animal in a rapid manner … the ideal signal would be light,” acknowledging at the time that his idea was “rather far-fetched.” In addition, scientists have been working on laying the foundation for this technology since the 1970s. For example, when Richard Fork, PhD, at Bell Laboratories in New Jersey at the time, published the stimulation of neurons in Aplysia with laser light in Science.

It was the discovery of the algal protein channelrhodopsin that led the way in making the vision into a reality. Microbial rhodopsins—found across archaea, eubacteria, and eukaryotic microalgae—harness light for cellular bioenergetics. Channelrhodopsin is found on the surface of Chlamydomonas, a single-celled alga with the ability to swim towards a light source. Researchers discovered that the protein can directly convert photon energy into transmembrane ion flux.

The first direct evidence of a light-gated ion channel was named channelrhodopsin-1 (ChR1), discovered and coined by the Hegemann lab. The arguably more consequential breakthrough came just a year later: a collaborative team led by Georg Nagel, demonstrated that a second protein, named channelrhodopsin-2 (ChR2), functioned distinctly from ChR1, and exhibited a blue-shifted activation spectrum and operated as a broad, non-selective cation channel.

Finding a microbial protein that could act as a single unit, simultaneously as a photoreceptor and an ion channel, and the discovery that ChR1 and ChR2 were single-component, light-gated ion channels, provided the precise tools that neuroscientists had been looking for—for fast, genetically targetable optical activation of neurons.

The team in the Deisseroth lab took the baton and performed the first successful demonstration that ChR2 could be expressed in neurons, using a construct provided by Nagel. They introduced the gene for channel-rhodopsin into nerve cells from rats and was able to trigger a nerve signal by illuminating the cells with blue light.

Deisseroth’s lab published this breakthrough in 2005 in the Nature Neuroscience paper, “Millisecond-timescale, genetically targeted optical control of neural activity.” The study demonstrated that expressing the microbial protein channelrhodopsin-2 (ChR2) from green algae in cultured mammalian neurons allowed precise, millisecond-timescale control of action potentials using flashes of blue light.

The paper’s first author was Ed Boyden, PhD, professor in Neurotechnology at MIT who has been developing the field of optogenetics for the past two decades. Interestingly, CRISPR pioneer Feng Zhang, PhD, is the second author on the 2005 paper. Two years later, Deisseroth’s lab made this light-controlled switch for nerve cells work in the brains of living mice.

Over the past two decades, optogenetics has been used to unpack many biological questions, primarily (but not exclusively) in the field of neuroscience. One early in vivo application of optogenetics probed the causal relationship between the activation of orexin/hypocretin neurons in the lateral hypothalamus and the transitions from sleep to wakefulness. Other notable applications were the search for the memory engram—the physical cellular substrate encoding a specific memory—and unpacking the complexity of dopaminergic neurons in the retina, showing that functionally distinct dopaminergic populations are anatomically intermingled yet strictly segregated by their circuit connectivity.

Optogenetics has also moved into clinical applications, such as the expression of ChR2 in retinal circuitry. In one experiment, intraocular injection of an adeno-associated viral (AAV) vector encoding ChR2 led to expression in retinal ganglion cells in rodents. More specifically, light depolarized the ChR2 expressing retinal ganglion cells, restoring retinal photosensitivity and allowing light signals to reach the visual cortex in a mouse model of retinitis pigmentosa. Expression of ChR2 in surviving retinal neurons could therefore serve as a potential strategy for restoring vision after rod and cone degeneration.

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The scientists say the research creates one of the most comprehensive reference maps of early human embryo development, which they used to benchmark the biological accuracy of stem-cell-derived embryo models. They systematically evaluated four leading human blastoid-generation methods and found substantial differences in how faithfully they reproduce the cell types and developmental processes seen in natural human embryos.

Pengyi Yang, PhD, associate professor at the University of Sydney and an ARC Future Fellow in the School of Mathematics and Statistics and Unit Head of Computational Systems Biology at the Children’s Medical Research Institute, said the work gives scientists a more objective way to understand the strengths and limitations of embryo models. “Human embryo models have enormous potential for studying the earliest days of an embryo’s development, but there has been no consistent way to assess how accurately these reflect real human development. Our framework allows researchers to compare these models against a detailed biological reference and determine which cell types and developmental processes are faithfully reproduced, and which are not.”

Yang, who also leads the Trans-Regulatory Biology group at the Charles Perkins Centre, is senior and corresponding author of the team’s published paper in Cell Systems, titled “Systematic transcriptomic evaluation of blastoid models of early human development.” In their paper the team stated, “The reference map generated from this study enables the benchmarking of blastoids that may guide the optimization of the protocol for the generation of high-fidelity blastoid models that faithfully recapitulate the natural human blastocyst.”

The study of early human embryogenesis from blastocyst formation to gastrulation has been constrained by what the authors describe as “… technical challenges and ethical concerns associated with human embryo research.” But research on blastoid embryo models, which are derived from stem cells, offers scientists a way to study the biological events that underpin fertility, pregnancy success, and early human development without relying on donated human embryos.

While these research models are not actual human embryos—current models cannot develop into a human embryo—they could help answer questions that have long been difficult to investigate because of technical and ethical constraints. “Recent achievements in generating blastocyst-like structures from stem cells, the blastoids, that are reminiscent of human blastocysts in morphology and cellular composition have opened an avenue to glean knowledge of the biology of early human embryogenesis,” the team continued.

However, just because something looks like an embryo, does that mean it is behaving like one biologically? The University of Sydney team developed a computational framework that helps answer that question. “Establishing a systematic evaluation framework for assessing the fidelity of blastoids in modeling the human blastocyst is critical for enhancing the quality of these stem cell-based embryo models (SCBEMs),” they noted. “… we set out to develop a computational workflow for systematically assessing how closely blastoids generated by current state-of-the-art protocols recapitulate human blastocyst cell states and develop mental features.”

To do this the team combined and harmonized more than 14,000 single-cell transcriptomes—the set of RNA molecules in a cell—from human embryos spanning key stages of their development. This allowed them to create a reference map of how cells normally differentiate and organize themselves during the days immediately before and after implantation.

The investigators then compared that reference against four widely used blastoid-generation protocols developed by international research groups. Rather than assessing whether the models simply resembled embryos under a microscope, the researchers examined their molecular identities, developmental timing, lineage structure, and other biological characteristics.

The results showed that some blastoid models reproduced all three major cell lineages of a natural human blastocyst, or the early embryo, relatively well, while others failed to accurately represent certain cell types or contained large numbers of cells that could not be confidently matched to any known embryonic state. No single model perfectly replicated a natural human blastocyst. “Results of the benchmarking revealed substantial differences between protocols in recapitulating the composition, developmental timing, and coordinated lineage specification of the human blastocyst, highlighting that high-fidelity SCBEMs should reproducibly generate appropriately staged and developmentally coordinated blastocyst cell states,” the authors reported.

Yang said the findings highlight both the promise and current limitations of embryo models. “The encouraging finding is that some models capture important aspects of early embryonic development relatively well, although each model has limitations,” he said. “But our study also shows that current models are not biologically equivalent to real human embryos, and researchers need to be careful about the conclusions they draw from them.”

By providing a standardized benchmark, the researchers hope future models can be improved more rapidly and evaluated more rigorously. “Collectively, our work provides a comprehensive and systematic evaluation of the developmental authenticity of in vitro cultured SCBEMs generated by the state-of-the-art protocols,” they concluded. “Yang added, “If we’re going to use these systems to answer important biological questions, we first need to know what they can reliably tell us. Our work provides a roadmap for improving embryo models and ensuring scientific claims remain grounded in what the models can actually support.”

The researchers have made their reference datasets and benchmarking tools publicly available, enabling scientists worldwide to test new embryo models against the same standards.

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Stuart Orkin, MD, and his former trainees Vijay Sankaran, MD, PhD, and Daniel Bauer, PhD, were joined by Swee-Lay Thein, MD, PhD, and John Tisdale, MD, both at the NIH. Their contributions helped to identify BCL11A as a major regulator of the fetal-to-adult hemoglobin switch, paving the way for the development of the first CRISPR medicine, Casgevy, for sickle cell disease (SCD) and thalassemia. 

Opening the symposium, HMS Dean George Daley, MD, paid tribute to Janet Watson, MD, the Brooklyn pediatrician who concluded in 1948 that fetal hemoglobin (HbF) was somehow protective against SCD. “The mechanism behind the switch would remain an enigma for decades,” Daley said.  

Each of the five honorees had “distinct and complementary roles” in the effort, Daley said, which culminated in the approval in December 2023 of Casgevy as well as Lyfgenia, a beta-globin gene therapy. Thein and Sankaran identified and characterized BCL11A as a critical regulator of HbF expression. Orkin and Bauer identified the enhancer sequence within BCL11A that controls erythroid gene expression and would become the specific target for Casgevy to restart HbF production. 

“We should hustle to make therapies that are simpler, safer and scalable,” Daley said. Bolstering newborn screening for SCD and expanding global distribution would be major steps to producing a bigger impact, such that “fewer people will have their lives upended by these devastating hemoglobinopathies.” 

Editing out disease 

The symposium’s keynote speaker—2020 Nobel laureate Jennifer Doudna, PhD—said, “Drug success requires a deep understanding of biology.” Having a functional cure for SCD less than 15 years after her team’s initial development of CRISPR-Cas9 gene editing was “just incredible,” she said. 

Doudna paid particular credit to patient volunteers such as Victoria Gray and Jimi Olaghere. “You can’t have success if you don’t have people willing to try it,” she said. According to Doudna, Casgevy is now approved in 39 countries across North America, Europe, and the Middle East. More than 90 percent of SCD patients in the U.S. qualify for reimbursement coverage for Casgevy. And more than 500 patients globally have begun Casgevy treatment.  

Naturally, challenges remain. Doudna focused on four: 1) Conditioning toxicity, 2) cost, 3) infrastructure, and 4) expanding global access. “How do we get from one CRISPR therapeutic to CRISPR-for-many? I think it’s achievable,” she said, citing the 2025 Baby KJ story as an example. In vivo gene editing will be critical in the future, Doudna said, but the toolbox for delivery is growing fast. She noted two recent preprints from her lab advancing novel strategies—NANITE and JET—as examples of works in progress. 

Beginning with BCL11A 

The symposium was organized by Ed Benz, MD, a renowned hematologist and President and CEO emeritus of the Dana Farber Cancer Institute. In SCD, the red blood cells (RBCs) become rigid and adhere to blood vessel walls. Tissues become ischemic resulting in pain crises and start to deteriorate. Many patients lose the function of key organs, especially the kidney, heart, and lungs. Life for people with SCD is “constantly dealing with pain, anemia, brain fog, etc. They rarely live a normal lifespan.” 

Orkin noted that this was not his first time winning the Alpert prize. He previously won in 1993 for his research providing a complete molecular genetic description of thalassemia. “A lot has happened in 33 years,” Orkin joked, noting profound changes in presidents, AI, and scientific landmarks.  

Orkin’s team has spent years defining the mechanism of BCL11A regulation of globin gene transcription, a process he likened to “going to the thermostat.” He highlighted a key paper along the way led by his former trainee Jian Xu, PhD, now at St. Jude Children’s Research Hospital. In 2011, Xu took an SCD mouse model, knocked out the Bcl11a gene in the erythroid lineage, and rescued the phenotype of RBCs. This prevented SCD symptoms and validated BCL11A as a therapeutic target in humans.  

The Casgevy results, Orkin said, were “spectacular… remarkable, transformative.” Orkin listed several advantages of the HbF reactivation pathway (as opposed to correctional gene therapy), including the validation provided by Casgevy; the balance of globin gene expression, and the fact it offered “one-stop shopping” for all hemoglobinopathies. But this ex vivo approach cannot reduce the global burden of SCD and thalassemia, Orkin said. Reasons include high cost, the complex nature of the process, and a lack of infrastructure. 

Still, the clinical success of Casgevy points to a clear target for small molecule drug discovery programs. “I argue that BCL11A is the preferred target,” Orkin continued. The protein acts directly on the gamma-globin promoter and has a steeper dose-response than other regulators, such as LRF. The protein “looks like spaghetti,” based on AlphaFold, Orkin said. It is an obligate multimer, which is critical for gene repression activity.  

Although highly stable, BCL11A is degraded in proteasomes as a monomer, raising the possibility that this pathway provides targeting opportunities for small molecules. “The goal should be development of therapies that can be delivered to the majority, if not all, patients with SCD and thalassemia,” Orkin closed. 

Oxford calling 

The focus of Thein’s research, beginning in Oxford when she joined Sir David Weatherall’s group in 1982, was a tantalizing question: Why are some patients with beta-thalassemia relatively mild and transfusion-independent? 

Thein focused on two large hemoglobinopathy families, finding high levels of HbF reduced the need for blood transfusions. She also found that HbF levels were independent of inherited mutations in the beta-globin gene.  

In 2007, Thein and colleagues performed a groundbreaking genome-wide association study (GWAS), looking at more than 5,000 participants of Northern European descent. Those with extreme phenotypes were genotyped using a panel of 300,000 single nucleotide polymorphisms. One of the three major signals was an unexpected signal that mapped to chromosome 2, which Thein further refined to the second intron of BCL11A. That unexpected signal eventually became a therapeutic target.  

Sankaran and Orkin independently confirmed Thein’s findings. That study was published in 2008 in Science. But how to go after BCL11A? Ironically, Sankaran observed, the answer was on the next page of the journal: a landmark paper in the early stages of CRISPR research published by Luciano Marraffini, PhD, and Eric Sontheimer, PhD. “I wish I’d paid more attention!” Sankaran quipped. 

Sankaran asked: How can we improve available hemoglobinopathy therapies globally? “We need to invest in all of these pathways—ex vivo, in vivo, and small molecules,” he said. With perfect timing, Sankaran’s team had just published an interesting new candidate for an HbF regulator—BACH2, which inhibits binding of NRF2. Although very early days, inhibiting BACH2 offers another intriguing drug target. “Much more biology remains to be understood,” he said. 

Gene replacement 

While the other four awardees played a role in characterizing the Casgevy pathway, Tisdale was recognized for his work as the lead clinical site for the Lyfgenia trial, sponsored by Bluebird.  

“When I hit the scene in the ‘90s, we had zero drugs to treat [SCD],” he said. The disease produces complications “literally from head to toe,” including strokes in children. The pain is so crippling that patients “can’t plan and can’t hold a job.” Building on the first allogeneic bone marrow transplant in 1996, by Mark Walters, MD, Tisdale’s group looked for less toxic chemotherapy options and established a non-myeloablative approach. 

“Luigi Naldini threw us a lifeline,” Tisdale said, with a report in Science in 1996 that lentiviruses could transduce non-dividing cells (like HSCs). Deleting the 3’ LTR reduced the risk of integration turning on adjacent genes. Tisdale’s group partnered with Bluebird for the HBG-206 clinical trial. While initial results were modest, in the Group C cohort, successfully treated patients behaved as if their disease had resolved to sickle cell trait. Lyfgenia was also approved by the FDA in December 2023 and is currently sponsored by Genetix Pharmaceuticals. 

Tisdale was asked how he counsels patients interested in signing up for gene therapy. “Most patients don’t understand the options,” he said. The discussion starts with a bone marrow transplant, but many insist they want gene therapy. “The first thing is to optimize hydroxyurea,” which is an inclusion criterion. “Most [patients have failed to try; many can improve that way, especially children.”  

Cognitive dissonance 

“Our field is facing a moment of cognitive dissonance,” said Bauer, in the fifth and final talk from the 2026 laureates. The excitement over gene therapies is balanced, he said, by “the frustration that current therapies are too complex to even dent the global burden of disease.” 

Bauer briefly described prime assembly, a new technology from his lab led by grad student Sebastian Levesque, which was published in Nature last month. The technology shows similar activity in dividing and non-dividing cells and “raises the prospect of mutation-agnostic gene correction for many diseases.” 

At the American Society for Hematology conference in 2016, Bauer recalled showing a slide of a mountain with several paths drawn to the top representing different potential approaches for treating SCD. He juxtaposed that slide with a photo of Casgevy trial volunteer Jimi Olaghere proudly standing at the summit of Mt. Kilimanjaro in 2024.  

The field has come a very long way, but still has further to travel. 

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Using live cultures of human brain cells and slices of brain tissue obtained during neurosurgery, the researchers, headed by Nicholas Barnes, PhD, professor at the University of Birmingham College of Medicine and Health, investigated the role of the P2X7 receptor, which is responsible for triggering inflammatory signaling. Their findings revealed that these P2X7 receptors drive the release of cytokines involved in controlling inflammation. By blocking this receptor with a specific antagonist, the team was able to significantly reduce the inflammatory response in human brain tissue.

The team suggests that their results could open the door to treating a wide spectrum of chronic neurological conditions, including TBI, neurodegenerative diseases, and even psychiatric disorders such as depression and psychosis, which are increasingly understood to have a neuroinflammatory component.

Barnes said, “This exciting discovery marks a major step toward repurposing existing therapeutics to combat neuroinflammation at its source. The identification of this receptor could have far-reaching implications for some of the most debilitating and widespread brain disorders such as Alzheimer’s disease, Parkinson’s, and multiple sclerosis, or inflammation-linked psychiatric conditions like schizophrenia and depression.”

Barnes is senior and corresponding author of the team’s published paper in Brain, titled “P2X7 receptor-mediated IL-1β release by human brain tissue: the impact of CNS-penetrant potential therapeutics,” in which they concluded “Our findings provide direct relevant evidence for the use of P2X7R antagonism to inhibit human microglia-mediated inflammation, with arising potential benefits for patients with TBI and other neuroinflammatory diseases.”

TBI is a major cause of death globally, and there are currently there are no approved therapeutic drugs to improve clinical outcomes, “… emphasizing the clear unmet substantial clinical need,” the authors wrote.

The mechanical damage associated with TBI drives a neuroinflammatory response. “The purinergic P2X7 receptor (P2X7R) is a key driver of neuroinflammation in a range of animal models of traumatic brain injury,” the team continued. P2X7R is expressed by microglia, the resident immune cells in the CNS that are involved in many developmental, homeostatic and pathological roles. “It is well recognized that microglial activation and the hostile neuroinflammatory response arising after the initial insult provide a therapeutic window for pharmacological intervention,” the investigators further stated.

For their reported study investigating how brain cells respond to and manage inflammation, the team developed a way of turning a type of white blood cell into microglia, replicating a normal cellular transformation that has recently been identified to occur in the brain as a natural part of human aging. These microglia are the central coordinators of the immune system in the brain.

Using readily accessible human peripheral monocytes taken from blood samples, the researchers converted them into microglia-like cells—human monocyte-derived microglia (hMDM)—that were used to see how microglia are likely to respond to the inflammation signals. “This enabled us to demonstrate the ability of clinically relevant P2X7R antagonists, including brain-penetrant molecules, to curtail pro-inflammatory cytokine release,” they wrote.

The team showed that administering a P2X7 receptor antagonist interrupted the triggers that these microglia give off as they are damaged and die. Barnes said, “Studying human microglia has long been a major challenge: once removed from their native brain environment, they rapidly lose their defining characteristics, likely due to the absence of critical regulatory signals. Our approach involved the use of monocyte-derived microglia which provide a powerful, scalable, and virtually unlimited platform for studying human microglial biology with unprecedented precision.”

The team confirmed their results using adult human precision-cut brain slices that had been generated subsequent to neurosurgical resections. “Having identified the response in the human monocyte-derived microglia, this provided the impetus to translate these findings with human brain obtained following neurosurgical procedures, Barnes continued. “This successful translation means the next stage for this research is the development of clinical trials in patients with neurodegenerative conditions and patients with TBI where there are no effective pharmacological treatments to reduce the neuroinflammation and arising damage.”

In their paper the authors concluded, “The present study provides direct translational evidence from human cellular and brain tissue models to support the clinical use of P2X7R antagonists to limit secondary ATP-driven neuroinflammatory events, such as those that occur in TBI, and thus might improve the clinical outcomes for patients.”

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Now, new research has revealed that bacteria detect viruses when a viral enzyme cuts an important sensor molecule in the bacterium, kicking off the immune response. Discoveries of bacterial defenses can pave the way for the development of better phage therapies that can evade the bacterial immune system.

The results are published in Science in the paper, “Phage proteases activate CBASS antiphage immunity.”

 “This is one of the most common forms of bacterial immunity, so when we finally figured it out, it was a total eureka moment,” said Sam Hobbs, PhD, assistant professor of biochemistry at University of Utah Health.

One component of the bacterial immune system is the cyclic oligonucleotide–based antiphage signaling systems (CBASS) which lead to a “last resort” immune response that kills the bacterium before viruses can spread to neighbors.

Precise sensing of the viral trigger is a necessity. In CBASS, cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes sense phage infection and synthesize nucleotide signals to initiate antiviral defense. This new work found that the sensing mechanism detects a molecule that the virus needs to survive. More specifically, that phage prohead protease activity is a widespread mechanism of CD-NTase activation.

“We found that the protease from the phage actually acts directly on the host protein, and that is the signal that turns on the whole signaling pathway,” explained Hobbs.

This trigger mechanism is distinct when compared to related antiviral immune pathways, which are activated by the presence of viral genetic material. “This is a totally new mechanism for how these host proteins are activated,” Hobbs said.

Hobbs added that understanding CBASS may advance our knowledge of the human immune system. CBASS is related to a similar immune pathway in humans, indicating that this pathway has persisted at least since bacteria and humans had a common ancestor. And because bacteria have such a rapid life cycle, scientists can use them to very quickly answer questions about how the immune system works, which they can then test in models closer to people.

“The fact that these systems are conserved between bacteria and humans suggests that they’ve been maintained in these different organisms for that entire evolutionary trajectory,” Hobbs said. “The cells are telling us that this is a really important pathway because they’ve maintained it for billions of years. It’s incredibly fascinating, and it’s a cool window into what’s important in maintaining the ability to fight viruses.”

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The New Jersey ASP is the 19^th to open globally, with the first launching in Japan and then expanding globally to facilities in places like China, the United Kingdom, and now the United States. 

During his opening remarks, Koutara Kato, executive vice president and assistant general manager, commercial operations, at HORIBA Instruments Incorporated, highlighted some of the industries that HORIBA is involved in, such as the semiconductor market, as well as where it plans to concentrate additional resources in future. That list includes energy and environment as well as biopharma and healthcare. Each area the company focuses on “gives us a lot of opportunities and challenges,” he said.

ASPs provide a space for HORIBA to apply its technology and scientific expertise to customers’ challenges and try to find possible solutions. It could especially benefit customers working with tight budgets amidst rising costs for lab equipment, space, and other factors, noted Michael Oweimrin, national sales manager at HORIBA, in his remarks. “We have a plethora of capabilities to address many different markets.” 

Over 280 heads at HORIBA report to the New Jersey facility which is about 130,000 square feet. And roughly 200 people work at the site. Among other features, the ASP features multiple labs, where HORIBA scientists work on customer projects as well as technical rooms for training application scientists. A key part of the ASP is its modularity. Instruments are placed or bolted to tables with wheels making it possible to move them seamlessly between labs as needed. 

A tour of a section of HORIBA’s facility, following the opening remarks and a traditional sake barrel opening ceremony, revealed space for stockrooms, manufacturing, and rooms testing and quality control as well as for training field service engineers. The tour included a look at the ASP labs where scientists leverage HORIBA’s expertise in instruments for modular spectroscopy, particle characterization, and Raman microscopy. Scientists in the ASP labs utilize these technologies to address applications in energy and environment, healthcare, and materials and semiconductors. They utilize HORIBA instruments including LabRAM Odyssey and LabRAM Soleil Raman microscopes as well as the Veloci Biopharma Analyzer, which is designed specifically for biopharma and pharma applications. 

Crucially, the ASP is HORIBA’s answer to an important question, Jeff Julien, PhD, life science applications manager at HORIBA, said in his opening comments. Specifically, “how to leverage what HORIBA does well” to shift the conversation from “what instrument is needed” to “what problem to solve.” Using biopharma as an example, he noted that companies developing therapeutic proteins often rely on input from multiple instruments and techniques during development. These are capabilities that the ASP scientists can provide, he said. 

As noted earlier, in each ASP lab, instruments sit on modular wheel-based carts and lab benches. This makes it possible to reconfigure the lab space for different customers’ pain points as well as to bring in technologies that  “we think could be applicable to those use cases,” Julien said. “It’s really an exciting time to be a part of HORIBA and doing this ASP development” particularly “as the markets change in terms of requirements and what customers are after,” he added. “It changes the way we think [and] the way we approach all of these problems.”

Shifting from sales to solutions

HORIBA’s ASPs  reflect a broader corporate strategy to move beyond purely transactional sales towards problem-solving partnerships. In the NJ facility, the focus is specifically in the life science and biopharma sectors. Here, HORIBA is positioning its core technologies as an underutilized set of orthogonal tools for various applications including biotherapeutic characterization.

To be clear, HORIBA’s primary business is still selling instrumentation, but moving forward, the company wants to do more to help customers utilize its instruments to solve problems, Kato said during a conversation with the press where he discussed some of the thinking behind setting up the ASP. “If a customer [is] facing some issues and difficulties, prior to having those instrumentation, we can address this” through the ASP, he said, by showing them how they can use HORIBA’s instruments and what kinds of outcomes they can expect. In most cases, to use the ASP’s capabilities, customers bring samples in and work with HORIBA scientists and tools. There are some cases where HORIBA can deliver needed instruments to customers’ labs to run their analysis on site.  

The company has no current plans to increase its headcount, rather it is leveraging expertise it already has in house to support customers looking to utilize the ASP’s capabilities. There are a few types of customer profiles that ASP scientists are working with and these typically are people working in research and development with specific pain points that they hope HORIBA’s fluorescence or Raman spectroscopy or its particle characterization capabilities could solve, Julien explained. 

Feasibility testing is a key step, often starting with simplified samples before graduating to real process samples. HORIBA emphasizes rapid pivoting between fluorescence, Raman, and particle characterization depending on what customer samples reveal. 

For example, “perhaps we’re anticipating [doing] a demo with fluorescence and we very quickly learn more about the customer samples or their process and then say … we need to pivot to Raman because that’s actually going to be a better fit for your use case,” he explained. Furthermore, “if we’ve exhausted our options in terms of what we think we can provide as a solution and it’s not meeting customer needs, we then can engage in conversation and … perhaps work together and develop a custom solution or a fit for purpose solution that’s going to meet those particular needs.”

HORIBA plans to launch additional ASPs in other locations—setups differ across the company’s offices. The strategy is one ASP per country in strategic locations rather than multiple per country, Kato said. This way, rather than having U.S. customers send samples all the way to an ASP in Japan, for example,, they can access a facility closer to them. ASPs are also customized to local industry needs, for example the ASP in Taiwan is semiconductor focused. The U.S. ASP leverages HORIBA’s location in the tri-state biopharma corridor. Conversations with company representatives highlighted HORIBA’s intent to make deeper inroads into the biopharma and life sciences market in particular.  

One area that the company is interested in broadening its footprint is in the biotherapeutics market. A key solution for the market is the Veloci Biopharma Analyzer which is designed for tasks such as analyzing antibody-drug conjugates, differentiating AAV subtypes, and for analyzing protein stability, among others. “We [are] now in an age where for a lot of therapeutics … [with] some of these stable technologies like near-IR that have been used historically … you’re infringing on the limits of detection for that technology” leading customers to seek out novel orthogonal measurement methods, Julien said. “That’s ultimately where we feel like we can add value.”

The company is working on some new products but HORIBA representatives declined to provide specific details about what they are.

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Deisseroth is a Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University and an HHMI Investigator; Hegemann is the Hertie Senior Research Chair for Neurosciences and a professor of Experimental Biophysics at Humboldt University and Nagel is a professor at the Department for Neurophysiology at the University of Würzburg, in Germany.

“Optogenetics provides opportunities for mapping the brain in a way that we could once only dream of,” says Per Svenningsson, MD, PhD, Chair of the Nobel Committee for Physiology or Medicine.

Although optogenetics is a relatively new technology, the seminal paper from the Deisseroth lab was published in 2005. However, the concept of manipulating specific neuronal cell types within intact circuits on a millisecond timescale was considered long before. Indeed, Francis Crick, PhD, once proposed a method where “all neurons of just one type could be activated or inactivated, leaving the others more or less unaltered.” He speculated that to “turn the firing of one or more types of neurons on and off in the alert animal in a rapid manner … the ideal signal would be light,” acknowledging at the time that his idea was “rather far-fetched.” In addition, scientists have been working on laying the foundation for this technology since the 1970s. For example, when Richard Fork, PhD, at Bell Laboratories in New Jersey at the time, published the stimulation of neurons in Aplysia with laser light in Science.

It was the discovery of the algal protein channelrhodopsin that led the way in making the vision into a reality. Microbial rhodopsins—found across archaea, eubacteria, and eukaryotic microalgae—harness light for cellular bioenergetics. Channelrhodopsin is found on the surface of Chlamydomonas, a single-celled alga with the ability to swim towards a light source. Researchers discovered that the protein can directly convert photon energy into transmembrane ion flux.

The first direct evidence of a light-gated ion channel was named channelrhodopsin-1 (ChR1), discovered and coined by the Hegemann lab. The arguably more consequential breakthrough came just a year later: a collaborative team led by Georg Nagel, demonstrated that a second protein, named channelrhodopsin-2 (ChR2), functioned distinctly from ChR1, and exhibited a blue-shifted activation spectrum and operated as a broad, non-selective cation channel.

Finding a microbial protein that could act as a single unit, simultaneously as a photoreceptor and an ion channel, and the discovery that ChR1 and ChR2 were single-component, light-gated ion channels, provided the precise tools that neuroscientists had been looking for—for fast, genetically targetable optical activation of neurons.

The team in the Deisseroth lab took the baton and performed the first successful demonstration that ChR2 could be expressed in neurons, using a construct provided by Nagel. They introduced the gene for channel-rhodopsin into nerve cells from rats and was able to trigger a nerve signal by illuminating the cells with blue light.

Deisseroth’s lab published this breakthrough in 2005 in the Nature Neuroscience paper, “Millisecond-timescale, genetically targeted optical control of neural activity.” The study demonstrated that expressing the microbial protein channelrhodopsin-2 (ChR2) from green algae in cultured mammalian neurons allowed precise, millisecond-timescale control of action potentials using flashes of blue light.

The paper’s first author was Ed Boyden, PhD, professor in Neurotechnology at MIT who has been developing the field of optogenetics for the past two decades. Interestingly, CRISPR pioneer Feng Zhang, PhD, is the second author on the 2005 paper. Two years later, Deisseroth’s lab made this light-controlled switch for nerve cells work in the brains of living mice.

Over the past two decades, optogenetics has been used to unpack many biological questions, primarily (but not exclusively) in the field of neuroscience. One early in vivo application of optogenetics probed the causal relationship between the activation of orexin/hypocretin neurons in the lateral hypothalamus and the transitions from sleep to wakefulness. Other notable applications were the search for the memory engram—the physical cellular substrate encoding a specific memory—and unpacking the complexity of dopaminergic neurons in the retina, showing that functionally distinct dopaminergic populations are anatomically intermingled yet strictly segregated by their circuit connectivity.

Optogenetics has also moved into clinical applications, such as the expression of ChR2 in retinal circuitry. In one experiment, intraocular injection of an adeno-associated viral (AAV) vector encoding ChR2 led to expression in retinal ganglion cells in rodents. More specifically, light depolarized the ChR2 expressing retinal ganglion cells, restoring retinal photosensitivity and allowing light signals to reach the visual cortex in a mouse model of retinitis pigmentosa. Expression of ChR2 in surviving retinal neurons could therefore serve as a potential strategy for restoring vision after rod and cone degeneration.

The post 2026 Nobel Prize for Physiology and Medicine Goes to Optogenetics, Light-Gated Ion Channels appeared first on GEN - Genetic Engineering and Biotechnology News.

With a famous biotech cluster in Research Triangle Park (RTP) established almost 70 years ago, North Carolina is already a powerhouse of pharmaceutical R&D and manufacturing, and recent expansion plans worth billions of dollars will continue growth into the future.

A delegation from the Biotechnology Innovation Organization (BIO), led by BIO President & CEO John F. Crowley, learned about North Carolina’s biotech industry on an Oct. 2 visit to RTP, a 7,000-acre complex spread across the three cities of Raleigh, Durham, and Chapel Hill, N.C. It was the latest stop of the BIO on the American Road learning and networking tour of America’s biotech ecosystems.

BIO’s delegation met local members of industry, patient advocates, and Rep. Deborah Ross (D-NC), a champion of IP rights and biotech (pictured at top, with Crowley). The BIO delegation also toured the RTP facilities of Biogen, which are currently undergoing a $2 billion expansion.

“Companies come to North Carolina and RTP because of the investments, talent, partnerships and strong support from elected leaders, like Rep. Ross, that make innovation possible,” said Crowley. “RTP has built an ecosystem where biotechnology companies can develop medical breakthroughs and manufacture them right here in America. The U.S. must continue to lead in biotechnology, and that requires building a stronger American biotech industry. North Carolina and RTP are demonstrating the power of bringing innovation, investment and manufacturing together.”

Biotech R&D, manufacturing, and distribution are all well represented in North Carolina, where the life sciences employed 103,107 as of 2024, according to a TEConomy NCBiotech report. These workers belonged to nearly 6,700 state businesses working in biotech, the report said.

BIO’s delegation met with several innovation leaders at an industry roundtable hosted at the offices of the North Carolina Biotech Center (NCBiotech). Founded in 1984, NCBiotech was the first state-sponsored initiative of its kind to support the biotech industry. They seek to “create North Carolina’s competitive advantage in the life sciences by engaging partners, maximizing opportunities, and delivering solutions to accelerate innovation, investment, and job creation.”

BIO also hosted a luncheon with patient advocates from across the state and met with  Rep. Ross, who represents the RTP area, at Biogen’s impressive manufacturing campus, which has roots dating back 30 years in the area.

Rep. Ross sits on the  House Judiciary Committee and has authored and supported several bills promoting IP and biotech.

Ross recently cosponsored H.R. 6089, the Biomanufacturing Excellence Act of 2025 which would establish a public-private partnership to allow innovators to scale their products in the U.S. with smarter, faster, more efficient manufacturing practices. The bill was inspired by recommendations from the National Security Commission on Emerging Biotechnology’s April 2025 Action Plan for Congress.

“I’m proud to represent North Carolina’s Research Triangle, where universities, startups, and major institutions are constantly pushing the boundaries of what’s possible,” Rep. Ross said. “That’s why I was grateful to visit Biogen’s RTP campus in Morrisville for an important discussion about the future of biomanufacturing in North Carolina. Biomanufacturing is a pillar of our economy and workforce, creating good-paying jobs and attracting some of the brightest minds to our community. It’s more important than ever that we develop new medications here at home that are accessible and affordable.”

‘Bipartisan support for biotech’

“Given the high level of biotech employment, the importance of the industry’s supply chain and research activities around the state, we see a lot of good bipartisan support for biotech from our federal delegation,” said Gunter.

She said NCLifeSci receives assistance and guidance from BIO when addressing federal issues that matter for North Carolina. These include: federal funding for the state’s top-tier research (R1) universities; SBIR federal seed funding for early-stage research; and national security priorities outlined by the NSCEB, Gunter said.

Founded in the early 1990s, NCLifeSci has focused on state policy affecting biotech.

“We’ve been able to have a real impact on the industry overall on the state level,” said Gunter. This has included “being one of the first states to really incorporate a matching fund for federal SBIR dollars,” getting state support for workforce development training programs, and tax incentives.

NCLifeSci was instrumental in establishing the NC Life Sciences Caucus, made up of lawmakers from both parties in both the state House and state Senate. Among its pro-biotech efforts, the Life Sciences Caucus supported the introduction of the first omnibus life sciences appropriation bill for inclusion in the state budget, NCLifeSci helped write the bill.

“Measures that matter to the industry were grouped in an omnibus package with the goal of saying, here’s a number of areas where the state can contribute to North Carolina’s life sciences,” Gunter said.

The pro-biotech policy environment and the existence of institutions like NCBiotech help North Carolina build one of the country’s leading biotech ecosystems, according to Gunter. Other attributes of that ecosystem include five R1 research universities, a broad range of small biotechs, a large concentration of clinical research organizations, and manufacturers—from major pharma firms to contract development manufacturing organizations.

“So we have the full soup-to-nuts of the biotech ecosystem, and it really works well together,” Gunter said.

Biogen’s growth

BIO’s team joined Rep. Ross for a tour of the RTP facilities of BIO member Biogen, a leading biotech company developing innovative treatments in neurology, immunology, and rare diseases. With more than 1,500 manufacturing and technical employees and more than 400 skilled contractors, Biogen is the largest biotech employer in North Carolina, and they’re still growing.

“Biogen announced a $2 billion investment in our existing Research Triangle Park (RTP), North Carolina manufacturing footprint in July 2025, and we’ve continued to progress this multi-project strategic investment plan since our announcement,” said Nicole Murphy, Biogen Executive Vice President and Head of Pharmaceutical Operations and Technology. “This year, Biogen’s facility in RTP has executed approximately $200 million year-to-date, supporting progress across multiple modality expansions, including a new ASO (antisense oligonucleotide) purification factory and additional synthesis capabilities.”

The expansion will also add new clinical product assembly and packaging capabilities, utility, environmental, and infrastructure improvements, continued digitalization and AI-enabled roadmap deployment, and initial engineering work for future biologics, fill-finish, lyophilization, and oral solid dose capabilities.

“The work happening here is helping Biogen reliably produce medicines for patients today while also building the capabilities we will need for the future,” Murphy said. “Given recent acquisitions, we are also evaluating additional potential investment opportunities based on our late-stage portfolio.”

While Biogen is headquartered in Kendall Square in Cambridge, MA, and has a new facility in San Francisco, it mainly conducts its U.S. manufacturing in North Carolina.

“RTP has become our largest manufacturing footprint because it offers the right environment for advanced biomanufacturing,” Murphy said. “You have leading universities, research institutions, life sciences companies and a deep technical workforce all in one region.”

Biogen is not just a beneficiary of the biotech expertise in RTP, it is also a major contributor to the ecosystem, Murphy noted.

“Biogen brings a large, established, and advanced manufacturing presence to RTP, along with continued investment in high-quality jobs, technical capabilities, and infrastructure. Our presence helps strengthen the broader life sciences ecosystem by creating opportunities for collaboration, training, and workforce development,” Murphy said. “We also work with local institutions and programs to help build pathways into biotech manufacturing careers, which is important both for Biogen and for the region’s long-term growth.”

Biogen’s North Carolina expansion is just one of several announced recently. Others include:

•  BIO member Genentech said it is planning to invest $2 billion in its first East Coast manufacturing facility in Holly Springs, NC.
• BIO member Novartis said in November it will build a flagship manufacturing hub in North Carolina, which will create an additional 700 jobs.
• AbbVie announced plans for a $1.4 billion manufacturing facility in North Carolina in April.

“North Carolina’s biotech sector is rooted in a long tradition of innovation, and its momentum continues to grow,” Crowley observed.

The post BIO on the American Road visits pioneering NC biotech hub appeared first on Bio.News.

Tariffs of up to 100% on patented pharmaceuticals and their ingredients that went into effect Sept. 29 are expected to increase costs for innovators, discourage drug development and investment, and potentially reduce patient access to drugs they need. They also weaken U.S. competitiveness at a time when China is seeking to replace America as the world leader in biotech, experts say.

Meanwhile, the lack of information on how to comply with the Administration’s guidance on tariff implementation is creating chaos that complicates day-to-day operations of drug makers, according to the biotech industry. Innovators of all sizes have questions, ranging from types of patents that will be considered to the process and criteria for seeking an exemption to the tariffs.

“With these tariffs, the United States has reversed decades of sound trade policy, creating new uncertainty for biotech innovators, and increasing the burden on the small- and mid-sized companies responsible for many of tomorrow’s breakthrough medicines,” according to a statement from the Biotechnology Innovation Organization (BIO).

As BIO research shows, small- to medium-sized biotechs are responsible for 71% of the industry’s output and 54% of the new drug applications. The smaller innovative companies generally have less available capital to adjust to shocks like tariffs or to take moves that could reduce the tariff burden, experts noted.

The tariffs are being implemented after a Department of Commerce Section 232 investigation determined that global supply chains are risky, and concluded that onshoring drug production bolsters national security. Yet, experts argue that the additional obstacles to global networks posed by the tariffs will weaken the supply chain and reduce our access to medicines we need.

Companies that agree to move their production to the U.S. can apply for reductions in tariffs, but this relief is out of reach for most small biotechs, which must outsource all of their production. Suddenly shifting their complex manufacturing processes from overseas contractors may be impossible, says Marta Wosińska, a senior fellow at the Brookings Institution, according to Axios.

These smaller firms also generally lack in-house capacity to adjust to new tariff reporting burdens for compliance, experts say.

Insufficient guidance

But even those firms seeking to comply do not have adequate guidance to do so, experts say.

As Bio.News reported on Sept. 14, with two weeks until implementation, much of the necessary federal guidance was still missing, including information on how to qualify for exemptions based on the type of drug being imported, the country of origin, and engagement in Most Favored Nation (MFN) pricing agreements or onshoring commitments.

On Sept. 23, days before the tariff went into effect, the Department of Commerce did issue new guidance, but “its guidance has created more confusion,” according to a Sept. 27 Wall Street Journal editorial.

“Biotech companies will have to apply for exemptions for each individual product, regardless of whether it meets one of the specified categories, and explain ‘why the import meets an urgent U.S. health need.’ Urgent will be in the eyes of the bureaucrats who rarely act with urgency,” says the editorial.

Indeed, the Commerce Department’s guidance does not seem to offer hard, fast rules on the definition of “urgent U.S. health need”, nor provide clarity on the criteria that Commerce will use to make case-by-case determinations.

“The rationale can include information such as the type of disease the product treats and an assessment of alternative therapies or lack of alternative therapies for the type of disease the product treats, the number of U.S. patients that use the product, and whether or not the product is available in other jurisdictions,” the Commerce department’s guidance says. While the guidance notes. “Commerce will make an individual, fact-specific, company-specific decision for each request.”

There is no set time frame for these decisions, and companies still don’t know if those that are ultimately granted exemptions will have to pay full tariffs first and ask for refunds later.

The challenge to competition

Experts expressed concerns that both tariffs and the cost of compliance will eat away at funding that could be used for research, harming America’s competitiveness and the future of innovative therapies for the American people.

“One small company says tariff compliance could consume 2% to 4% of its working capital before it commercializes its first medicine,” says The Wall Street Journal’s editorial. “That means less money for research. It’s hard enough developing a new drug. Tariffs add more uncertainty that will discourage investment in U.S. biotech.”

While the justification given for the tariffs is strengthening national security, experts worry that by harming America’s ability to invest in biotech research, it will have the opposite effect.

“At a time when the United States should strengthen its biotechnology leadership to compete aggressively with China, these tariffs move us in the wrong direction,” says BIO’s statement.

The post Tariffs’ drag on innovation compounded by lack of guidance, experts say appeared first on Bio.News.

“We all believe that there is a shared risk factor of aging for many, many chronic diseases. But to me, it’s interesting: Is there a way of beginning to start quantifying that, really working a lot on the biological side but also on the clinical side, what that looks like?” FDA Chief Scientist Steven Kozlowski, MD, told attendees at the 13^th Aging Research & Drug Discovery Meeting (ARDD 2026), held at the David Rubinstein Treehouse at Harvard University.

Kozlowski said the updated FARS would come out early in FY 2027 but offered no further specifics on timing.

“It would be really good to have a shared endpoint [that was] pre-competitive, qualified, and shared broadly so that everybody can use that can serve as a bridge,” Kozlowski elaborated. “Attributes of that endpoint would be regulatory acceptance, right? You buy into that endpoint and it’s really useful, that it allows feasible clinical trial designs that it’s worth doing, that it serves as a standard for all the other novel things that come after it, and that to some extent helps with accessibility [to other researchers].”

Kozlowski spoke during “Matching Clinical Trials of Therapeutics & Regulatory Mandates,” a panel of four current FDA officials.

“Steve and his team have been working really hard to develop these key areas where I’ve been speaking to all of our stakeholders where there is a need for more regulatory science,” said Lowell M. Zeta, JD, Acting Chief of Staff in the FDA’s Office of the Commissioner. “To the extent that we can be and should be evolving our programs to help you all solve the challenges, that’s what we want to hear.”

Zeta called longevity and healthspan—the number of years a person lives free from long-term disease or disability—“an important topic for the agency and HHS [U.S. Department of Health and Human Services].

‘A defining moment’

“It’s really a defining moment, an inflection point for the future,” Zeta added. “It’s a test for the future of FDA and how to adapt to the rapidly evolving science in this space.”

Zeta was the highest ranking FDA official on the panel, which included Justin Penzenstadler, PharmD, acting associate director of the FDA’s Office of Cardiology, Hematology, Endocrinology, and Nephrology; and Jeffrey Siegel, MD, director of the FDA’s Office of Drug Evaluation Sciences.

Panel moderator was Andrew Brack, PhD, program manager, proactive health with ARPA-H. Brack oversees PROSPR (PROactive Solutions for Prolonging Resilience), a $144 million research initiative designed to extend American healthspan by redefining how aging and functional decline are measured and treated.

Brack began the panel session by asking a question to the four FDA officials: What do you see as the most realistic regulatory path to date response of trying to develop a therapy that targets aging biology rather than a single disease?

Siegel replied that aging could be considered for approval of new therapies in two ways. One is taking into account that aging increases the prevalence of numerous chronic diseases, including types of cancer, Parkinson’s disease, Alzheimer’s disease, and cardiovascular disease.

“Once you get to two or three that the same mechanism impacts, you begin to think that maybe this general mechanism is having an effect overall on aging-related disorders. And maybe you would be able to generalize from that,” Siegel said

Impact on people

But there is another approach, Siegel continued, which entails looking at the ways that aging impacts people, such as increasing the risks of cognitive decline and frailty, and causes loss of senses such as hearing and vision.

“If you have a way to evaluate those general aspects of aging, and you can define a patient population who’s subject to that aging-related deterioration, then you have to make use of a clinical trial that could demonstrate an effect on aging more broadly,” he explained.

The trial would need to measure aging-related domains, showing that the progression of these domains is less in treated patients than in an untreated control group, Siegel said: “That would be an indication that this is impacting the way that patients function and feel and survive, and potentially could be a way towards demonstrating efficacy for a drug impacting aging.”

Basic science research in recent decades has identified general mechanisms that underlie the aging process. Experimental models blocking some of these mechanisms has been demonstrated to increase lifespan, sometimes by as much as 30%, Siegel explained.

‘Amazing implications’

Some newer studies, he added, have suggested that treatments that block these aging processes could potentially reverse aging.

“If this can be applied in therapeutics for people, this has amazing implications, potentially increasing lifespan, but also decreasing the adverse effects that aging has on people, including aging-related diseases.”

Officials and researchers have long ascribed economic as well as health benefits to lengthening healthspans: An economic analysis published in 2021 concluded that a slowdown in aging that increased life expectancy by one year would generate $38 trillion in economic gains—a figure that ballooned to $367 trillion for 10 years of increased life expectancy.

Siegel said earlier trials will look at prevention of age-related comorbidities or mortality as an endpoint, but will also collect measures of clinical outcome assessments. He cited drug development history: The first trial of insulin evaluated a single patient—a 14-year-old boy with type 1 diabetes—using a single endpoint, mortality.

“I see geroscience following a similar arc, where you start with enriched patients, you’re looking at the hard endpoints, right? And then as the field, the body of evidence builds, you’ll be able to say, hey, here’s some measures that track with mortality. And maybe we ought not run trials as long,” Penzenstadler said. “You might be able to start validating some other endpoints or biomarkers that predict mortality, and that could shorten your trials.”

The FARS focus on aging and longevity sparked a question from a panelist in the panel that followed.

“Let’s say aging will be designated as a disease, how do we define it? And suddenly we come to a decade-long question, what is aging?” asked Steve Horvath, PhD, professor, human genetics and biostatistics at University of California, Los Angeles (UCLA).

Huge progress

“I would say we’ve made huge progress in defining that. And in short, it’s complicated, but you will not—in my opinion, you will not be able to get there unless you also have molecular biomarkers of aging,” Horvath asserted. “Assessing function in 10 different ways and disease indication, that’s really easy and very well defined. But what can we, the scientists in the field, contribute to physiologic markers, molecular markers of aging, so that they can be folded into future clinical trials that target aging per se?”

The 2022 FARS report—completed within the tenure of then-FDA commissioner Robert M. Califf, MD, who served under Democratic presidents Joe Biden and Barack Obama—was written with the COVID-19 pandemic still fresh in recent memory. That explains why the first priority highlighted by that report was “Public Health Preparedness and Response.” Also identified were:

• Increasing Choice and Competition through Innovation.
• Understanding the Power of Data.
• Empowering Patients and Consumers.

The terms “aging research” and “longevity medicine” do not appear in the 2022 FARS.

According to the FDA, a key purpose of FARS reports is to communicate the importance and impact of its ongoing regulatory science research activities that cut across its numerous centers, offices, and laboratories. The FDA defines regulatory science as the science of developing tools, standards and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products.

The FDA is now helmed by Acting Commissioner Kyle Diamantas, JD, who previously served as the agency’s deputy commissioner for food. President Donald Trump has nominated Heidi N. Overton, MD, PhD, as permanent commissioner. Overton’s nomination has yet to be voted by the U.S. Senate, whose Committee on Health, Education, Labor, and Pensions heard testimony from her on September 24.

Urging disease prevention

Before the FDA panel Admiral Brian Christine, MD, HHS assistant secretary for health, urged longevity drug developers and researchers to focus on modifying biological processes associated with aging over time and intervening to prevent disease before it occurs, rather than managing illness once someone gets sick.

Christine—who was appointed by President Donald Trump, confirmed by the U.S. Senate, and serves under HHS Secretary Robert F. Kennedy Jr.—aligned the push toward longevity medicine articulated by panelists at ARDD 2026 with Kennedy’s “Make America Healthy Again” (MAHA) policy framework. Kennedy has led an overhaul of federal policy on nutrition and disease prevention including vaccination schedules, prompting backlash from medical groups and researchers. David Robert Grimes, PhD, a professor of biostatistics at Trinity College Dublin and advocate, last year characterized MAHA as a movement that “thrives on science denialism.”

Not so, according to Christine.

“At its core, our MAHA movement is about confronting chronic disease,” Christine contended. “It begins with a very simple question, deceptively simple: Why are so many Americans sick, and what are we willing to do differently about it?”

“For decades, we have too often responded to chronic disease one condition at a time, and frequently, unfortunately, measure the rate and course of the disease,” said Christine, who also leads the U.S. Public Health Service Commissioned Corps, which consists of about 5,300 public health professionals. “Good science must be willing to ask questions even when the answers challenge longstanding assumptions. That matters enormously in healthy aging because patients are already moving faster than many traditional institutions.”

He cited as examples growing interest by women in menopausal hormone replacement therapy, by men in testosterone replacement therapy, and by both in improving their health through peptides, dietary supplements, continuous glucose monitors, wearables, biological AIDS tests, and emerging diagnostic technologies.

“Increasingly, people are learning about these interventions from podcasts, from social media, from wellness clinics, and direct to consumer companies before they ever walk into a physician’s or a nurse’s office,” Christine said.

Christine and the FDA officials spoke during ARDD 2026’s initial series of sessions. Before they spoke, George Q. Daley, MD, PhD, dean of Harvard Medical School, opened the conference with a plea for caution when it comes to promoting the benefits of drugs designed to fight the effects of aging.

“I’m concerned that the optimistic claims being made by some in the aging community far exceed what one can responsibly conclude from our current understanding of the biology,” Daley told ARDD 2026 attendees. “I implore you all to listen attentively to the many compelling presentations scheduled over the next few days, but also skeptically and critically, so that we will emerge with a greater respect for the science, but proper restraint in forward-looking claims of life extension.”

The post FDA to Highlight Aging, Longevity Medicine in Planned FARS Updates appeared first on GEN - Genetic Engineering and Biotechnology News.

Scientists exposed mice to a predator odor after giving them a placebo or a cannabinoid drug. Animals given the cannabinoid froze more and spent less time investigating the odor. Using small microscopes, scientists identified neurons activated by the drug that helped drive anxious behaviors. When those neurons were silenced the cannabinoid no longer triggered the same level of anxious behaviors.

The findings could help scientists better understand how cannabis exerts its psychoactive effects, and potentially point to strategies for holding back anxiety in affected individuals. The results could provide insights into strategies for reducing anxiety symptoms in other contexts, outside of cannabis use.

“The results of this study could explain why a good trip can turn bad pretty quickly if people consume too much cannabis or the situation they are in turns stressful or scary,” said Sachin Patel, MD, PhD, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine.

Patel is senior and corresponding author of the team’s published paper in Nature Communications, titled “Cannabinoid modulation of central amygdala population dynamics during threat investigation.” In their paper the team concluded that their results “… could ultimately provide important insights into how cannabinoids augment threat reactivity and the interactions between cannabis use and anxiety disorders.”

Plant-derived cannabinoids are widely used for medicinal and recreational purposes, and exert broad-ranging behavioral and physiological effects on mood, anxiety, memory, appetite, and sleep, the authors noted. But they can also precipitate anxiety and panic reactions in people, and increase threat-related defensive responses in rodents. “Specifically, while tension and anxiety relief represent major reasons for cannabis use, paradoxical dose- and context-dependent increases in anxiety and panic are also well-documented, and some studies have suggested associations between cannabis use and the development and worsening of anxiety disorders, especially in heavy cannabis users.” However, they continued, Despite well-established research findings, “… how cannabinoids affect in vivo neural dynamics associated with threat-related behavior has not been examined.”

For their newly reported study the scientists exposed mice to a threatening odor. Before being exposed to the scent, derived from fox urine, the mice either received a placebo or a synthetic cannabinoid drug. Patel and colleagues tested several doses of the synthetic cannabinoid on mice and tracked how much time they spent near the predator odor, and whether they froze or fled from the scent.

To simultaneously record brain activity, the team implanted a small microscope into the mice’s brain. The results showed that mice receiving the cannabinoid drug froze more often and spent less time investigating the predator odor. These anxious behaviors were linked to the drug’s activation of a small group of somatostatin neurons (SOM) in the brain’s central amygdala (CeA), a region that processes fear and stress.

Importantly, when the scientists genetically silenced the somatostatin neurons, mice given the cannabinoid drug did not avoid the predator scent as much. The researchers also conducted brain tissue experiments to analyze how the cannabinoids affected interactions between neurons. They found that the drug weakened the brain’s natural “brake” on the somatostatin neurons, allowing them to become more active. “Our data suggest suppression of GABA release from local afferents onto CeA SOM neurons underlies cannabinoid effects on CeA SOM neurons,” they wrote.

“Higher doses of cannabinoids and environmental stress worked together to synergistically release the ‘brake’ on the central amygdala, which in turn drove excessive anxiety,” Patel noted. “Understanding how cannabis affects brain function to generate its psychoactive effects could ultimately reveal new ways to counteract negative consequences should they arise in some people,” Patel said, also noting that the findings could have implications beyond cannabis. “Suppressing the activity of somatostatin neurons in the central amygdala could represent a final pathway for reducing anxiety symptoms, not just in the context of cannabis side effects,” he explained.

Cannabis use in the U.S. has steadily increased in recent years and so have emergency department visits related to adverse effects from the drug. Previous studies have also found an association between cannabis use and increased risk of anxiety in the long term. What’s more, anxiety and mood disorders are also on the rise globally.

Commenting that their newly reported data begin to shed light on neural mechanisms subserving the “dark-side” adverse effects of cannabinoids, the authors concluded, “… we suggest cannabinoids could trigger context-dependent adverse anxiety and panic reactions, in part, via activation of CeA-related circuits and that cannabis-induced long-term adaptations in these circuits could contribute to observed associations between cannabis use and anxiety disorders.”

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But the tool that delivered it matters just as much: an upconverting nanoparticle (UCNP) probe, doped with heavy rare earth elements, that simply doesn’t photobleach.

In one corner of Sam Peng’s lab, the imaging rig looks almost improvised. Cameras, lenses, and lasers are bolted directly onto a metal breadboard, like an enormous sheet of Legos built by hand rather than bought off a shelf.

Peng’s team engineered UCNPs doped with ytterbium, erbium, and thulium to track EGFR, HER2, and HER3 at the single-molecule level on live cells simultaneously, in three colors. The new imaging platform holds 100-millisecond resolution and runs for over 16 minutes straight. Conventional dyes lose signal within seconds. These UCNP probes do not photobleach.

Peng compares short-duration imaging to eavesdropping on a conversation that gets cut short: “If you’re trying to understand a conversation between two people… if all of a sudden I just cut off this conversation, then you have to guess my answer based on our previous two-minute interaction, which is often impossible to do.”

The real advantage isn’t a fixed window. Peng said the probe can run for hours. His team stopped at 16 minutes because they’d already captured the long EGFR homodimers they were after.

HER3’s stable pairing

The surprising finding was the unexpected stability of HER3 homodimers and the effects of cancer-associated mutations on these pairings.

“The first time we saw HER3 homodimers, we were really puzzled,” Peng told GEN. “We thought that maybe this was some experimental artifact.”

HER3’s kinase domain is too weak to signal on its own, so the prevailing model treated it as a heterodimer partner—something that pairs with other receptors. This does not rule out its forming homodimers. Peng’s team expected HER3 to serve as a negative control for dimer detection. It should have come back empty.

The team reran the experiment with different labels and probes. The result held every time: wild-type HER3 homodimers proved remarkably stable, far outlasting unstimulated EGFR homodimers.

The group’s working model is that these homodimers form a signaling-inactive pool. In this model, they sequester HER3, limiting its availability to pair with other receptors and trigger cancer signaling.

Cancer mutations support the model, but EGFR and HER3 moved in opposite directions. Mutations like the exon-19 deletion make EGFR homodimers more stable, driving signaling that tracks with clinical aggressiveness. The more stable the dimer, Peng said, the more signaling it triggers. The HER3 mutations studied do the opposite, destabilizing the homodimer, potentially freeing HER3 to form signaling-active heterodimers.

HER2 rounds out a third pattern. The HER2 mutations studied only modestly enhance the stability of its homodimers. That tracks with the clinic: HER2 cancers are typically driven by gene amplification.

Sourcing the materials 

Ytterbium and erbium are heavy rare earth elements. Unlike light rare earth elements such as neodymium, mined at industrial scale for electric vehicle (EV) motors and consumer electronics, heavy rare earth elements are produced in far smaller volumes, for a narrow set of high-performance uses where few substitutes exist. Peng’s imaging platform is one of them.

The supply chain for these materials is highly concentrated. China dominates global rare-earth separation and refining, and its share of the heavy subset is larger still. According to Benchmark Mineral Intelligence, China controlled 85% of total rare earth oxide production in 2025, including an estimated 99% of dysprosium oxide and terbium oxide. That concentration has shown up in prices for those magnet metals: in 2025, dysprosium oxide in North America on average cost 4.4 times the Chinese price.

China introduced export controls on seven rare earth elements in April 2025: samarium, gadolinium, terbium, dysprosium, lutetium, scandium, and yttrium. An October 2025 expansion added ytterbium, erbium, holmium, thulium, and europium, including the elements used in Peng’s probes. That expansion is currently suspended under a U.S.–China trade truce.

At bench scale, Peng’s lab works in milligrams to grams, small enough that global supply pressure doesn’t immediately register. His lab buys rare earth salts in vials from a U.S. distributor. “They come in as a form of powder, like salt, just like your kitchen salt,” he said. Erbium salts arrive in pink. “Pretty beautiful,” he noted.

An expertise gap, not a supply gap

Heavy rare earth elements aren’t especially scarce in the earth’s crust. They’re just rarely found in concentrations worth mining—and separating them is difficult. While Peng’s lab doesn’t track where the material was mined, it likely comes from China.

Peng’s lab buys these salts the way other labs buy antibodies. Rare earth elements are used in TR-FRET, some forms of NIR-II imaging, mass cytometry, and UCNP tracking, although these methods use different elements and probe chemistries.

As Xi Jinping was recently in Washington for his first state visit in more than a decade, U.S. officials said the two sides had agreed to extend their trade truce, and with it the pause on China’s expanded rare earth controls, from November to January.

Currently, the bottleneck is expertise, not supply. Peng estimates roughly a dozen groups worldwide work at this intersection of UCNP imaging and single-molecule biology. It’s a small overlap, since the work demands nanomaterial chemistry, molecular labeling, advanced optics, and computation, all in one lab. “It’s the integration of this entire pipeline that makes it challenging,” Peng said.

The research of nanoparticle optics has lasted for years. For now, the rare earth salts are the easy part. The optics, and the people who can build them, are what’s scarce.

References

1. Broad Institute. Single-molecule tracker illuminates workings of cancer-related proteins. Broad Institute of MIT and Harvard. Published May 1, 2026. Accessed September 24, 2026. https://www.broadinstitute.org/news/single-molecule-tracker-illuminates-workings-cancer-related-proteins

2. Shida JF, Ma K, Toll HW, et al. Multicolor long-term single-particle tracking using 10 nm upconverting nanoparticles. Nano Lett. 2024;24(14):4194-4201. doi:10.1021/acs.nanolett.4c00207

3. Peng Lab, Broad Institute of MIT and Harvard. Accessed September 24, 2026. https://www.sampenglab.org/publications

4. Ingall G, Mukherjee N. Ex-China rare earths premium to grow, especially for heavies. Benchmark Mineral Intelligence. Published March 24, 2026. Accessed September 24, 2026. https://source.benchmarkminerals.com/article/ex-china-rare-earths-premium-to-grow-especially-for-heavies

5. Shalal A. US, China agree to extend trade truce by two months, work on bigger deal, Bessent says. Reuters. Published September 23, 2026. Accessed September 24, 2026. https://www.reuters.com/world/asia-pacific/us-treasurys-bessent-chinas-he-meet-unfinished-business-before-trump-xi-summit-2026-09-23/

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This week, I officially signed up for an unusual competition. One that rewards competitors for getting younger.

I recently turned 40, and I don’t need reminding that both time and my chronological age only tick forward. But this game is focused on competitors’ biological ages—figures that are meant to provide a better way to measure the age-related health of our organs and bodies.

Over a six-month period, around 500 of us will try to reverse our biological age as measured in a bunch of different ways. There’s even a leaderboard! The winners will include the person who shows the greatest difference between their chronological and biological age, as well as the person who manages to reverse their biological age the most.

The competition is the brainchild of the neuroscientist and physician Christin Glorioso, who is also founder and CEO of NeuroAge Therapeutics. The company offers tools to track brain health and aging and is running a trial to find out if biological brain age can predict the onset of Alzheimer’s disease.

Glorioso says she has several goals for the Younger contest. The first, she tells me, is to “explain to the world what aging clocks are.” Regular Checkup readers will be familiar with these tools, but for the uninitiated, they are basically designed to measure biological age.

Many measure chemical signatures that form a layer on top of our DNA and seem to change with age. But others might involve looking at proteins or lipids in blood. Some are designed to measure functional health, while others predict when a person will die. There are more than a hundred clocks out there, and they probably each capture a specific aspect of the biological process of aging.

These clocks are proving very useful for scientists, who use them to study aging and development in humans and many other species. But using them to estimate the biological age of an individual person is more controversial. They’re just not good enough for that yet.

Part of the problem is that we don’t really understand what each clock is capturing. Glorioso hopes that data collected through the Younger contest might help answer that question. She’s hoping to generate “the world’s most comprehensive clock dataset.”

Some longevity clinics try to get around the limits of biological age testing by using multiple clocks. That’s this competition’s approach too. As a standard competitor, I’ll be sending a blood spot sample to TruDiagnostic, a company that measures epigenetic chemical groups on DNA and offers to reveal an overall biological age as well as a person’s pace of aging and the biological ages of each of 11 organ systems, including the heart and brain.

I’ll get a brain age score from NeuroAge once I complete the cognitive tasks on offer. I’ll also submit some physical measures like grip strength. And I’ll upload a series of selfies to an app developed by a team at Harvard that promises to tell me my face age. That’s exactly what it sounds like—an estimate of how old my face looks.

I’m intrigued to see my scores, even though I know I shouldn’t put too much stock in them. The first time I took a test, four years ago, the company I used gave me a biological age that matched my chronological age, which was a little disappointing and, if I’m honest, a bit underwhelming. A year later, the same company told me I had a young heart but a relatively old brain, liver, and hormonal system. My lifestyle hasn’t changed much since then. Will the years have made much difference?

(Ultra competitors—who pay $4,499 rather than the $999 cost of regular entry—are also offered a range of other blood tests and clocks, as well as MRI and DEXA scans. I’ve got complimentary press access to the standard package.)

Glorioso is also hoping to gather information about the effects of some purported longevity approaches. During the competition, some participants will be offered red-light masks, access to a sauna, or other low-risk offerings that partner companies who are sponsoring the event to varying degrees might want to collect data on. “A lot of these companies just can’t afford to run [clinical] trials,” says Glorioso.

She also sees the event as a public health initiative. A couple of years ago, David Sinclair, who studies aging at Harvard Medical School, and his colleagues estimated that if we could slow down aging in the general population and increase life expectancy by one year, it would save the US economy $38 trillion.

The event officially kicks off in January, but around 120 people have already signed up, says Glorioso. Ultimately, she expects 500 participants. Each person’s six-month run starts as soon as they take their baseline measurements, whenever that may be. A handful of people have already started. “I think the majority of people are going to want to sign up after the holidays,” says Glorioso. “They’re not going to want to be trying to win an aging contest over Christmas and Hanukkah.”

Glorioso took her own baseline measurements back in August. Those initial tests suggested that her biological age was around 10 years below her chronological age. That sounded pretty impressive to me until I looked at the leaderboard and saw that competitor @Fred had a biological age 28.8 years below his chronological age.

The leaderboard is pretty sparse at the moment, as only seven people have logged their baseline measurements so far. Six of them have biological ages tracking low, but one 47-year-old has been given a biological age of 68.1. She’s competing publicly, so I can see the breakdown of her scores. The worst is for the speed at which she can stand from sitting in a chair—by that measure, she’s been given a biological age of 100.

Hillary Lin, a longevity-focused physician in New York, has just started logging her baseline measurements for the competition. She tells me she’s taken biological age tests in the past and that they’ve tended to give scores below her chronological age, which is currently 37. Last year, the TruDiagnostic test put her pace of aging at 0.75—suggesting she’s only doing nine months’ worth of aging in a typical year. “That’s supposed to be quite good,” she says.

If it had been up to her, Lin says, she would have incorporated more blood tests into the competition, to build a fuller picture of a person’s health. And she’s worried that a six-month period might not be long enough to see changes in biological measures of aging. Still, she’s excited, and is already making plans to improve her sleep, diet, and exercise.

But she already follows a high-protein, low-carb diet and works out at the gym every day. She also visits a sauna every few days (sauna use has been linked to improved heart health). Glorioso’s efforts are impressive too. She tells me she’s started drinking a smoothie made from a pond plant that has been linked to health improvements, and that she’s cut added sugar and deep-fried foods from her diet. She’s also bought “a bunch of fancy Korean sunscreens” in an attempt to lower her face age.

I haven’t received my kit or logged my baseline measurements yet, and I’ll wait until then to start setting health goals. I don’t fancy my chances against these two competitors. But at the very least, I hope I can stand up faster than a 100-year-old.

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

That adaptability is one of several defenses that make Acanthamoeba infections difficult to eliminate. The pathogen can also retreat into a drug-resistant cyst, and the treatments available once an infection is diagnosed are limited and may damage human cells. By mapping the organism’s mitochondrial proteins, researchers now have a new way to probe the machinery behind its survival and search for more selective therapeutic targets.

“It’s a big challenge. The lack of readily available diagnostics is a problem, and then even after you finally get to the diagnosis, we don’t have good drugs,” said Jon Stefely, PhD, a metabolism investigator at the Morgridge Institute for Research and assistant professor of biomolecular chemistry at the University of Wisconsin School of Medicine and Public Health. “Our current drugs are untargeted and toxic, and we just need more options for treating these infections.”

To begin expanding those options, Stefely and his colleagues created a high-confidence inventory of the proteins operating inside Acanthamoeba castellanii mitochondria. The experimentally defined mitoproteome reveals the pathogen’s metabolic flexibility while highlighting potential therapeutic vulnerabilities. Their paper, “Mitochondrial proteome of Acanthamoeba delineates aerobic and anaerobic pathways dynamically regulated by oxygen,” was published in Cell as part of the MitoCarta Tree of Life Consortium, along with their other paper published in Cell Press Blue, “Acanthamoeba castellanii genome reannotation and multiomic encystation profiling reveals cyst wall proteins and carbohydrate-active enzymes.” The consortium was conceived by Vamsi Mootha, MD, of the Broad Institute, Massachusetts General Hospital, Harvard Medical School, and Howard Hughes Medical Institute; Stefely completed the work as a postdoctoral researcher in Mootha’s laboratory.

In their Cell paper, the researchers first improved the organism’s nuclear genome annotation—important because most mitochondrial proteins are encoded in the nucleus—from about 52% accuracy to 98% using long-read RNA sequencing and other empirical methods. “If you imagine a page of words in a book, it would be like all the words were squished together and in a language that you don’t know,” said Stefely. “You would have to ask, ‘Where are the words? How do I separate one word from the next?’ It’s hard to tease apart.”

They then combined mitochondrial immunoprecipitation, density-gradient purification, microscopy, mass spectrometry, and protein-correlation profiling. Proteins that became enriched as mitochondrial samples grew purer were assigned to the organelle. Blue native PAGE–mass spectrometry for complexome profiling further resolved 20 macromolecular assemblies.

The resulting AcMitoCarta catalog contains 1,122 proteins, including 381 without readily identifiable counterparts in human or yeast mitochondria. Just over 300 were described as unique when compared with those organisms. Such divergence could matter for drug discovery: a compound directed at a microbe-specific protein or pathway may be less likely to damage human cells. “What’s been proven historically,” Stefely said, “is that if you have a target protein in a biochemical pathway that’s completely unique to the microbe, it’s a better target than something that has a homolog in humans.”

Proteomic and transcriptomic profiling also showed that oxygen extensively rewires the amoeba’s bioenergetic machinery. Under oxygen-rich conditions, its mitochondria use aerobic pathways; under anoxia, they induce a pyruvate:ferredoxin oxidoreductase-to-hydrogenase pathway. The researchers demonstrated that eye-infection-derived Acanthamoeba cells can produce hydrogen gas without oxygen through a mitochondria-localized, oxygen-sensitive hydrogenase. That metabolic switch may help the organism persist in changing niches, including the cornea.

AcMitoCarta now provides a framework for testing which of these unusual proteins are essential to amoebal survival, cyst formation, or oxygen adaptation. Stefely plans to investigate the candidates and pathways in focused groups, with collaborators contributing expertise in mass spectrometry, RNA sequencing, metabolism, structural biology, and imaging. “A long-term goal is to annotate functions for all of those targets,” he said, “but we’ll take them one small set at a time and there is a lot of potential for new discoveries.”

The catalog does not yet identify a ready-to-use drug, but it narrows the search to experimentally supported mitochondrial components and pathways that differ from those in people. By moving from an incomplete genome annotation to a functional map of oxygen-responsive mitochondrial biology, the work lays a foundation for more selective treatments against an infection whose toughest form can withstand today’s therapies.

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“My big excitement when I was starting my independent career was trying to ask the question, ‘could these new technologies actually help us unlock these undruggable targets?’” he told GEN in an interview. “There is a lot of interest in this problem” of cracking challenging targets as well as in turning the findings into “something that has an impact in the real world and patients.”

Those early roots put him on the path that led to co-founding Talus Bioscience, a company that uses artificial intelligence (AI) to enable drug discovery for the disordered proteome, alongside Lindsay Pino, PhD, who also serves as the company’s chief technology officer and leads the development of the company’s screening platform.  In addition to being a co-founder, Federation is also the company’s CEO. He credits Pino with introducing him to proteomics as an effective approach for taking on the undruggable target problem.

This week, Talus released Ptarmigan-1, a solution powered by the company’s MARMOT platform, which it describes as a first-of-its-kind structure-free AI model that accurately predicts small molecule binding sites across the entire human proteome, including proteins that are too unstructured for traditional 3D modeling tools to resolve. MARMOT stands for Measuring Modulation of Transcription and is the underlying experimental assay that captures snapshots of proteins in their cellular environment without removing or tagging them.

On a separate note, the company’s name and the names of its products are somewhat whimsical as they are drawn from Seattle’s mountains and wildlife. But there is a link to the core challenge that company is taking on. Talus refers to a precarious boulder field requiring careful navigation which is a metaphor for navigating disordered proteins. Marmots and ptarmigans are wildlife that are native to the mountains—a possible reference to Talus’ way of measuring proteins in their native state. 

Talus’ approach focuses on the approximately 40 percent of human proteins in cells that lack stable, defined 3D structures and cannot be studied or targeted using conventional structural biology methods. Outside cells, they fall apart, making them difficult to purify or analyze using standard experimental workflows, Federation noted. Even advanced AI tools like AlphaFold render these proteins as uninterpretable structures. 

“Our platform is essentially a unique way to actually watch what these proteins are doing in the cell in their native state without having to take them out of the cell and letting them fold and function within that native environment where all their partners are,” he explained. “That gives us really for the first time the ability to see them in their native state and find molecules that can interact with these proteins in their native state.” 

Importantly, the company’s technology is label free since adding tags to these proteins changes their dynamics. In a sense, it’s “like we’re taking a cell and taking snapshots of where the proteins are at any given time and what molecules are sticking to those proteins at any given time,” he said. “And we use these new label-free proteomics methods as our camera to take those snapshots. That’s the fundamental measurement that we’re taking.”

The company has adopted a two-pronged business model. First, they have identified a small number of targets that they are developing molecules for internally. The most advanced molecule in their pipeline targets a rare bone cancer called chordoma. Specifically, they are targeting the brachyury protein, which is encoded by the TBXT gene. This particular protein is typically only expressed in embryonic stem cells; the cancer reactivates it. Simultaneously, the company is open to partnering with other companies to work on targets in a range of disease areas.

Finding molecules for invisible protein pockets

Ptarmigan-1 is the first version of Talus’ flagship structure-free model, and also a first of its kind AI model, according to its developers. There have been some approaches that have tried to accomplish similar goals, “but this is the first one that will actually tell you if a compound binds and where on the protein it binds,” Federation said.  

For targeting transcription factors, which Talus is interested in, this is an important capability. Despite clear biological validation of the disease relevance of transcription factors in disease, going after them as potential drug targets has proven to be an intractable challenge. It is “the type of target where the biology is so clear,” he said. “[W]e need molecules that can control these, and this is really the first step to make that possible.”

Ptarmigan-1 differs from other AI drug discovery tools, which rely on fitting a molecule onto a defined protein pocket. By eliminating the structure requirement entirely, Ptarmigan is designed to target the approximately 40% of the proteome, including many disease-relevant transcription factors and regulatory proteins that are flexible and lack a 3D structure that could be targeted by therapeutics developers. With this release, “we want to get a first tool out there that can really broaden the landscape … beyond just those structure targets,” Federation said. “We are excited for people to be able to take that and apply it broadly to the proteins that they care about.”

Talus has shared some results from a proof-of-concept study where they used Ptarmigan-1 to evaluate a STAT6 inhibitor series, a validated target for inflammatory disease with a hard-to-model binding site. The results showed that the model outperformed structure-based methods in selecting successful drug candidates even though it had not seen the target or molecules during training. The model also identified small molecules that bound to the flexible pocket on STAT6. These candidates were validated in a third-party lab. 

“The data we’re building at Talus is structure-agnostic, meaning we can measure proteins whether or not they hold a fixed shape,” Pino said. “That means the model can learn just as well from flexible or intrinsically disordered proteins as it does from structured ones, which is what lets it generalize to targets nobody’s had a way to study before.”

Details of the AI model are provided in a preprint that describes its architecture and the data that went into training it. Rather than forcing proteins into a 3D structural space, Ptarmigan embeds proteins and compounds in a shared high-dimensional mathematical space and then identifies candidate compounds by proximity in that multidimensional space. The model also has a speed advantage over other methods based on internal benchmarks from the company. They claim that since it skips the protein folding process, it runs 5,000 times faster than structure-based methods, and is capable of screening over three billion compounds against the human proteome in a day. 

Ptarmigan-1 is currently free to scientists through a public portal. Users will be able to run a limited number of experiments for free using the platform. But for expanded usage or larger target-specific campaigns that are a heavier lift computationally, Talus is open to direct collaboration for example, partnering with a company that has validated targets and an existing assay but lacks viable molecules. 

Collaborations will make it possible to do “some of these really massive searches that allow us to break into that really novel chemical space” and “search screens on the order of billions of compounds.” Also, “we hope someday when we have the next iterations of these [AI models] to be able to partner on those as well,” Federation said. Oncology is one the company’s primary interests, but the Talus team is also interested in targets in immunology, neurology, and cardiometabolic disease. 

The company is committed to ensure scientists have continued access to the model by maintaining a free-access tier for our Ptarmigan models over the long term. As of today, Talus Bio has announced $28M in venture and non-dilutive funding. 

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“We usually think of the body clock, the response to temperature, and the response to food as separate systems,” said Gerhart-Hines. “A mitochondrial transporter that is tuned by the time of day, the temperature, and what we eat raises the possibility of therapies that shift when and how the body burns fuel. That would be a different kind of lever from today’s obesity and diabetes treatments.” Gerhart-Hines is co-corresponding author of the researchers’ published paper in Science, titled “Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of adipocyte lipid cycling.”

“The circadian clock synchronizes physiological processes with environmental cues, integrating signals from sunlight, diet, physical activity, and temperature to optimize metabolic function across tissues,” the authors wrote. Brown adipose tissue (BAT) burns fuel to make heat, and this activity is controlled by the body clock, dropping during sleep and rising before waking. “In mice and humans, BAT metabolic activity begins to increase just before waking, peaks late in the waking period, and then declines to its lowest point during sleep,” the team noted.

However, a cold morning or a skipped meal makes demands the clock never planned for. How the body keeps to a fixed energetic timetable while still improvising has long been a puzzle. “How thermogenic fat can seamlessly achieve both rhythmic continuity and acute responsiveness is a fundamental question of energy homeostasis that has remained unknown,” they continued.

For their reported study to investigate this, the researchers started by searching large datasets for proteins in mouse brown fat that respond to both the clock and the cold. They identified UCP1, the best-known heat-producing protein, and SLC25A34, a related transporter with an as yet unknown job. In mice kept comfortably warm, brown fat contains less SLC25A34 than almost any other organ. But after 24 hours in the cold its levels rose 90-fold, making brown fat the tissue with the most SLC25A34 in the body.

To work out how the Slc25a34 gene is controlled, the team studied mice engineered to lack specific regulatory proteins. They found three separate controls, each answering to a different signal. A clock protein, REV-ERBα, keeps it switched off during sleep and releases it before waking. “During the sleep phase, the adipocyte clock suppresses Slc25a34 expression through the REV-transcriptional repressors,” the authors explained further. “When animals wake and REV-ERB circadian repression is lifted, the peroxisome proliferator–activated receptors α and γ (PPARα and PPARγ) αre able to bind the Slc25a34 promoter and restore expression.” Cold also lifts the brake at any hour, overriding the schedule when extra heat is needed. And fat, from the tissue’s own stores or the diet, switches the Slc25a34 gene on through another protein, PPARα. “… at any time, when animals are suddenly confronted with an unanticipated need for adipocyte energy expenditure such as exposure to cold temperatures or eating a lipid-rich meal, REV-ERB repression is rapidly overridden and PPARs are activated by lipolytic signals to boost SLC25A34 levels. When the energy demand is met, the REV-ERB–mediated rhythmicity of Slc25a34 is reestablished.”

Seemingly paradoxically, both fasting, which promotes using fat, and insulin, the hormone that promotes building fat, increase SLC25A34 levels. This means that signals for burning and storing fat run through the same transporter. However, this is explained by the fact that active brown fat actually builds new fat molecules to then burn, a cycle that generates heat and clears fat and sugar from the blood. SLC25A34 appears to keep the cycle turning by carrying a molecule called oxaloacetate back into the mitochondria. “Our biochemical and metabolic data support a functional model in which SLC25A34 transports oxaloacetate into mitochondria,” the authors noted. Without the transporter, brown fat cells burned less fuel, and in mice the tissue’s fat-burning response was significantly weaker. The team has yet to show directly that the transporter carries oxaloacetate, or what losing it means for long-term health.

The researchers also found that silencing the transporter in brown fat cells from three of four human donors also reduced their fuel burning. Across 24 clinical studies, people with more SLC25A34 in the white fat beneath their skin tended to be leaner and metabolically healthier. This result is an association and does not prove cause, the team points out.

“Many of these mitochondrial transporters still have no known function,” said first author Iuliia Karavaeva, PhD. “This one turned out to be needed both for building fat and for burning it. And we are only scratching the surface: SLC25A34 is also highly expressed in the heart and is implicated in brain and liver metabolism, but what it does in those organs remains a mystery.”

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A new AI tool can guess what you’re looking at just by analyzing your brain scans—and re-create that image with remarkable precision. It can go the other way, too, and predict a person’s brain activity based on what they’re looking at. 

In the image above, for example, the left-hand image of each pair is what the user actually saw—and its right-hand counterpart is what the model reconstructed from the brain scan.  

Michal Irani, who developed the tool with her colleagues at the Weizmann Institute of Science in Rehovot, Israel, hopes her “mind-reading” tool will ultimately reveal more about how the brain works, and could perhaps be used to help locked-in people communicate, or allow scientists to re-create the content of dreams. 

Judy Illes, a neuroethicist and professor of neurology at the University of British Columbia in Canada, who was not involved in the research, describes the work as “magnificent.” “The idea [of using this approach] to help people with neurologic conditions … therapeutically is tremendously exciting,” she says.

But other scientists warn that a similar approach could be used to reveal people’s inner thoughts and mental imagery, potentially without their consent. “The results seem very impressive,” says Tommy Sprague, a neuroscientist at the University of California, Santa Barbara. “But if there’s a way to surreptitiously extract information about what you’re thinking about, then …1 50 years of sci-fi can come true anytime, and that’s worrisome in a lot of ways.”

Peeking into the brain

Neuroscientists have been working for years on ways to use functional magnetic resonance imaging (fMRI) to reconstruct what people see and what’s going on in their minds. The first attempts produced images that were blurry and hard to make sense of. Advances in technology—both in the fMRI scans themselves and in the tools used to make sense of the results—have led to improvements over the years.

Irani and her colleagues started by analyzing publicly available brain-scan data. Other researchers had already collected scans from volunteers who were shown hundreds of images while they lay in fMRI scanners.

fMRI uses a giant magnet to track the flow of oxygenated blood through the brain. Brain areas that “light up” on the scans are thought to be those that are particularly active at any given moment. The results are not especially specific—in typical fMRI scanners, each highlighted “voxel” of activity covers around three cubic millimeters, containing around 16,000 neurons.

But Irani and her colleagues used newer datasets collected using scanners with a higher resolution—each voxel covered around one cubic millimeter of neurons, she says. Those datasets showed what the brain activity of volunteers looked like when they viewed various images.

Other teams have done this too, and several other tools have been used to re-create images from brain-scan data. But they’re not good enough, says Irani. Say a person saw a banana. These models can generate an image of a banana, but it would look different, she says. “It wouldn’t have the same structure, the same position.”

A better decoder

The researchers  wanted to more closely re-create the images that had been seen. The first step was to train an AI model on already available data from eight people who each had been shown around 9,000 images while in a high-resolution fMRI scanner.

Crucially, their “brain decoder” has two branches—one to predict the structure of an image (where the colors are, for instance) and a second to predict its content (for example, a bunch of bananas on a plate). The predictions allow a diffusion model, a type of AI best known for creating video and images by gradually cleaning up a noisy mess of pixels, to produce a much more accurate representation of what the person saw.

But to improve the models they needed more data—far more than was actually available.  

To get around this problem, Irani and her colleagues trained another model—an encoder that can predict brain activity from an image. The team then used the encoder and decoder together to improve both tools.

It works like this: Start with a new image of, say, a leopard. Then use the encoder to predict what someone’s fMRI brain scan would look like when the person saw that picture. The decoder is then used to reconstruct the image. At first, the reconstruction probably won’t look much like a leopard, says Irani. But repeatedly training the models this way eventually leads to dramatic improvements.

This approach also allows the team to train their models on as many images as they want, even images that have never been shown to a person in an fMRI scanner. Irani says that around 70% of the training data is from images that were not originally paired with fMRI scans.

By combining data from multiple studies, they were also able to identify brain regions that seem to share functions across all individuals. One region seemed to respond to images of food, for example, while another responded to images of sports. Irani, a computer scientist, says she is now working with neuroscientists “to see if we can actually use these tools that we’ve developed to really find out new things about the brain.”

The resulting “universal brain encoder” can work on a scan from a new person with minimal calibration. In other attempts, a tool has typically required about 40 hours of fMRI data on anyone new before it can be used to predict what that person is seeing. Irani’s decoder only needs one hour of data, she says. The finding was presented at the Cognitive Computational Neuroscience conference in New York last month.

That could make it valuable for neuroscientists studying the brain, says Sprague. “None of us can afford 40 hours of imaging for a new subject,” he says. “It’s something like $600 to $1,000 an hour.” Tools like this one could speed up research, he says.

State of the art

The encoder and decoder aren’t perfect. “Of course we have failures,” says Irani. Over a Zoom call, she pointed out an image of a cake that her tool reconstructed as a pile of three sandwiches, and another of a dog in a bathtub that was reconstructed as a similarly colored goat in a bathtub.

But they represent the state of the art. In a comparison test, the tool was found to be much better than previously described ones. “All in all, really we outperformed the others by a significant margin,” Irani says. “Mind reading” is a “cute, jazzy name” for what they’re doing, she adds.

Irani is now planning to move beyond images to video and audio. She wants to be able to reconstruct what people are thinking about or imagining, and the contents of their dreams. “That’s something we don’t have yet,” she says. “But we’re striving to achieve it.”

Such a tool might enable people who are “locked in” and completely paralyzed to communicate using their brain activity alone, she says. It could also help scientists unpick some enduring mysteries surrounding the inner workings of our minds, such as what PTSD flashbacks look like.

Advances like this inevitably raise questions about mental privacy. What if some bad actor could reconstruct someone’s thoughts or memories?

“If you’d asked me that 10 years ago, I’d have laughed a lot,” says Sprague. Getting a willing person to lie still in a scanner and actively engage with a research question is hard enough; imagine making someone do it involuntarily. But Irani and other scientists are working on similar approaches to decode brain activity from EEG—electrical brain activity measures collected via a cap of electrodes or even through headphones. 

And as models improve, it will become even easier to analyze the brain activity collected this way. “We have to be a little more serious about the ethical considerations,” says Sprague. He thinks Irani’s approach would probably “work quite well” in predicting images that a person is thinking about but not looking at.

The move to EEG would be a “game changer,” says Marcello Ienca, a neuroscientist and philosopher at the Technical University of Munich, Germany. Once an EEG device has been calibrated to a user’s own brain, it could be relatively easy for companies to extract additional information from that person’s brain—potentially without consent. Ienca can also imagine some courts allowing mental image reconstructions as legal evidence.

“I have no doubt that this is, you know, well-intentioned research, but I think it’s also pretty obvious that it could be co-opted for … ethically and societally problematic commercial uses,” he says.

Irani acknowledges the potential for misuse with the use of EEG. But she’s not concerned for now. “I’m trying to think only of good things,” she says.

Affinity is important, but it is not a drug profile. A peptide must also be selective, soluble, synthetically tractable, sufficiently stable, and able to reach the relevant biological compartment. Depending on the program, it may need to cross a membrane, remain extracellular, internalize into a specific cell type, or sustain activity after transient exposure. A screen that reports only binding leaves these questions for later, when changing molecular direction is more expensive.

The next advance will not come from choosing experimental screening over computation, or computation over screening. It will come from designing experiments so that each round produces a more informative map of the chemical and biological landscape.

Library is already part of the hypothesis

A peptide library is never truly unbiased. Its length distribution, residue alphabet, cyclization chemistry, topology, display format, and synthesis method determine which molecules can be produced and which conformations can be explored. These choices also influence stability, solubility, permeability, and presentation of binding groups.

Peptide function is not encoded by sequence alone. Two molecules with similar residue composition can behave differently when one is linear and the other is cyclic, when stereochemistry changes, or when a backbone amide is modified. For constrained peptides, linkage position and ring topology can reorganize the conformational ensemble. A sequence-only analysis may therefore group together molecules that are chemically and pharmacologically distinct.

Recent work illustrates the opportunity. A 2026 study screened 15,360 fully random, sub-kilodalton cyclic peptides and identified a starting point against the intracellular Keap1–Nrf2 protein–protein interaction. Iterative design, synthesis, and testing produced a membrane-permeable inhibitor active in living cells. The broader lesson is that binding and permeability can be treated as connected design problems rather than sequential hurdles.

Screen in biological space, not only against a target

Purified-protein screens remain useful, particularly when material is limited or throughput is essential. But the assay format can become an unintended selection pressure. Peptides may recognize a purification tag, a surface, an exposed hydrophobic patch, or a conformation poorly represented in the native setting. High apparent affinity can also reflect nonspecific interactions that disappear in another assay.

The solution is not to force every primary screen into a complex cellular system. It is to design a staged assay hierarchy before screening begins. Early counterselections can remove binders to tags, matrices, related proteins, or abundant off-targets. Competition experiments can test dependence on the intended epitope. Homolog counterscreens can reveal selectivity within a target family.

Orthogonal confirmation through kinetic binding, solution-phase competition, biochemical function, or cell-based activity can distinguish reproducible target engagement from assay-specific behavior.

For intracellular programs, permeability and functional activity should enter the workflow as soon as candidate numbers permit. For extracellular targets, serum stability, target turnover, tissue context, and the consequences of sustained versus transient engagement may matter more. The objective is not to measure every property immediately, but to ensure that the screening cascade reflects where the molecule must ultimately work.

Most screening readouts are snapshots. Biology is not. An endpoint measurement can obscure differences in association rate, dissociation rate, target rebinding, internalization, degradation, or intracellular retention. A peptide with modest equilibrium affinity but a slow off-rate may produce stronger functional activity than a tighter binder that dissociates rapidly. Conversely, prolonged engagement may be undesirable when an off-target interaction creates risk.

Time can be incorporated in practical ways. Selection pressure can be increased by extending wash periods or adding soluble competitor. Candidates can be tested after defined exposure to serum, proteases, reducing conditions, or relevant tissue fluids. Cellular assays can separate immediate pathway modulation from activity that persists after washout. Internalization and cytosolic access can be measured at multiple time points rather than inferred from one image.

Round-by-round enrichment also contains temporal information. A sequence that rises steadily may be more credible than one that appears abruptly after a bottleneck. Intermediate sequencing data can reveal early enrichment, late artifacts, and architecture families that respond differently as selection pressure changes.

Preserve the reasons molecules fail

The final hit list is often the least informative version of a screening dataset. It contains the winners but discards much of the evidence needed to understand why they won.

For peptide programs, “inactive” is not a single label. A candidate may fail because it was not produced efficiently, did not display correctly, was not cyclized or otherwise modified, aggregated, degraded, bound nonspecifically, failed to enter cells, or reached the target without changing function. These outcomes should not be collapsed into one negative class. A model trained on them would be asked to learn biology from a mixture of technical and pharmacological failures.

Useful datasets require provenance. Starting-library abundance, enrichment by round, control behavior, counterscreen results, synthesis yield, purity, modification efficiency, assay conditions, batch identity, and detection limits should travel with each sequence. Missing values also need interpretation. “Not detected” can mean below an assay threshold, absent from the starting population, lost during processing, or simply not tested.

Physics-based modeling and machine learning are often presented as competing approaches. In peptide discovery, they are more useful when assigned complementary roles.

Physics-based calculations can examine conformational ensembles, intramolecular hydrogen bonding, solvent exposure, target contacts, and the consequences of a specific substitution. They are especially valuable when experimental data are sparse or a mechanistic explanation is needed. Their limitations include computational cost, sampling challenges, and sensitivity to the underlying model.

Machine learning can recognize relationships across larger datasets, rank candidates, propose combinations a human team might not prioritize, and support multi-parameter optimization. Recent work has coupled generative models with Bayesian optimization and prospective synthesis and testing to improve peptide scaffolds under experimentally defined constraints. Deep-learning methods are also becoming more capable of cyclic-peptide structure prediction and redesign, although limited training data remain a central challenge.

The most productive workflow uses physical insight to define plausible chemical space, experimental data to anchor predictions, and machine learning to identify the next informative measurements. Optimization should not collapse every objective into one opaque score. Teams should examine trade-offs directly: a modest loss in affinity may be acceptable if it produces a major gain in selectivity, stability, permeability, or manufacturability.

Build the learning strategy before the first hit

An integrated peptide campaign can be organized around five decisions. First, define the intended product profile early. Target compartment, route of administration, dosing expectations, selectivity requirements, and minimum functional effect should shape the screen.

Second, make molecular architecture an explicit variable. Sequence diversity matters, but diversity of constraint, stereochemistry, backbone composition, and topology may reveal different solutions to the same target.

Third, establish the assay hierarchy and controls in advance. Primary enrichment, counterscreens, orthogonal binding, functional activity, and developability measurements should answer distinct questions rather than repeatedly measure the same one.

Fourth, retain complete and interpretable data, including technical failures and uncertain outcomes. Computational methods cannot repair labels that confound failed production with failed biology.

Finally, test models prospectively. A model that explains an existing dataset may still fail on new architecture classes or assay conditions. The meaningful test is whether it selects the next peptides better than established heuristics—and whether those results improve the following round.

The output of a peptide screen should not be viewed only as a ranked list. It should be a calibrated map showing which sequences and architectures succeed under which conditions—and where uncertainty remains.

That map can reveal whether a target favors a particular topology, whether a stability gain repeatedly costs function, whether a permeability strategy generalizes, and which measurements best predict cellular activity. It can also prevent teams from optimizing an impressive binder that was never compatible with the intended medicine.

Peptide discovery will continue to benefit from larger libraries and more capable algorithms. But scale alone does not guarantee learning. The programs that move most efficiently will treat library design, screening, functional biology, physics, and machine learning as parts of one experimental system—built not merely to find a winner, but to understand how to make the next molecule better.

Karsten Eastman, PhD, is the CEO and co-founder of Sethera Therapeutics.

The post Designing Peptide Screens to Generate Knowledge, Not Just Hits appeared first on GEN - Genetic Engineering and Biotechnology News.

The results present a promising new treatment target for autism spectrum disorder (ASD) symptoms. “The road from discovery to clinical trials is long, but we’re excited by the possibility that our findings might one day improve the daily lives of people with autism,” said Baptiste Lacoste, PhD, senior scientist at The Ottawa Hospital and professor at the University of Ottawa.

Baptiste is senior author of the team’s published paper in Neuron (“Purinergic receptor activation rectifies autism-associated endothelial dysfunction”), in which they concluded “These findings suggest that P2Y2 receptor activation represents a promising strategy to rescue brain EC dysfunction and, in turn, improve autism-related behaviors in the 16p11.2 deletion ASD syndrome.”

Autism is a neurodevelopmental condition with widely varying characteristics. Some of the behavioral symptoms can make life more challenging. While many people with autism have found ways to manage these symptoms, no drug treatment exists.

Lacoste’s team previously discovered that blood vessels in the brain don’t work properly in mouse models with a 16p11.2 deletion, one of the most common genetic mutations seen in autism. They were the first to look at what was happening in the blood vessels of the brain. “Recent evidence in a 16p11.2 deletion mouse model of autism spectrum disorder (ASD) revealed brain endothelial abnormalities postnatally, but the endothelial alterations eliciting these changes remain unknown,” they wrote.

Through their newly reported work the researchers have now found that the problem began in the endothelial cells lining the blood vessels. These cells make sure blood quickly gets to the parts of the brain that are active. This responsive blood supply is needed for proper brain function.

However, the endothelial cells in the 16p11.2 deletion mice don’t respond quickly enough. This happens early in brain development and causes behavioral symptoms later in life, including hyperactivity, repetitive movements, and motor learning impairment.

Headed by former PhD student, Julie Ouellette, PhD, the research team looked at what was wrong with these endothelial cells and whether it could be fixed. They discovered that the cells had half the normal level of ATP. “We demonstrate that 16p11.2 deletion induced EC dysfunction is caused by a bioenergetic failure with reduced intracellular ATP,” they explained. While ATP is usually considered an energy molecule, in this case the cell was missing its target, called a P2Y2 receptor, on its surface. “The identified energetic failure was restricted to ECs, emphasizing these cells as key contributors to ASD pathophysiology,” the investigators added.

By activating this P2Y2 receptor, the researchers were able to restore the cell’s function, increase blood flow in the brain, and reverse the behavioral symptoms in adult mice. This was achieved using a drug known to activate P2Y2 and which is currently approved for humans in Japan and South Korea to treat dry eye syndrome.

“Activation of ATP signaling via endothelial P2-class purinergic receptors, specifically P2Y2, rescued EC dysfunction, restoring angiogenic capacity in vitro, endothelium-dependent cerebrovascular reactivity ex vivo, and activity-dependent cerebral blood flow (CBF) in vivo,” the team stated. “A selective pharmacological P2Y2 agonist also rescued adult 16p11.2-deficient behavioral phenotypes.”

Lacoste said, “It’s as if these cells are asleep, and now we can wake them up. And we may only need to treat them once to wake them up permanently. We will test that further, but it’s an encouraging feature for a future treatment.”

In their paper the authors concluded, “Taken together, this study demonstrates that metabolic reprogramming of brain ECs via purinergic receptor engagement represents a promising therapeutic avenue for ASD.” They also point out that the study only looked at adult mice. This means targeting P2Y2 could reverse behavioral symptoms that were already well established.

Next, the team plans to treat mice earlier in life to see if early treatment has additional benefits. The team has also filed a patent application for using P2Y2 activation in the blood vessels to treat autism symptoms. They are interested in exploring drug development with the aim of eventual clinical trials.

The post Autism Target Discovered in Endothelial Cells in Genetic Deletion Mouse Model appeared first on GEN - Genetic Engineering and Biotechnology News.

Purna Kashyap, MBBS, director of the Mayo Clinic Microbiome Program and Bernard and Edith Waterman Director, Microbiomics Program, Mayo Clinic Center for Individualized Medicine, and Ruben Mars, PhD, a microbiome researcher at Mayo Clinic in Minnesota, are co-corresponding authors of the researchers’ published paper in Cell, titled “Microbiome signatures linked to cancer and treatment adverse events in a real-world cohort.”

“The gut microbiome reflects an individual’s environment, lifestyle, diet, and physiological state, making it a sensitive barometer of overall health,” the authors wrote. Increasing evidence is implicating the gut microbiome in cancer biology, pointing to links between composition and function to disease development and treatment outcomes. “As the field shifts from association to causality, a key challenge is prioritizing microbes and pathways most likely to drive specific cancers.”

For their reported study the investigators conducted a real-world study of 1,364 Mayo Clinic Cancer Microbiome cohort patients with different cancer types, before starting a new treatment. “This cohort captures the diversity of cancers and treatments encountered in clinical practice, providing a robust foundation for uncovering microbiome signatures specific to individual cancers,” they wrote.

The investigators compared the cancer patients with 287 people without cancer to identify broad microbiome differences. Comparisons across cancers then revealed more specific signals. After accounting for other health conditions, researchers pinpointed 341 bacterial species associated with five cancer groups.

Among those, neuroendocrine tumors showed a broad loss of common health-associated gut bacteria. Liver and intrahepatic bile duct cancers had higher levels of several bacteria, including Enterococcus faecalis. Esophageal cancer had higher levels of six species, including Streptococcus bacteria. Distinct links were also found in lymphoid leukemia and multiple myeloma and related plasma cell cancers.

“We can now narrow the search to those microbial changes that are most specific to individual cancers,” said Mars. “Those are the signals we need to understand first if we want to determine whether the microbiome plays a causal role in cancer and ultimately develop targeted interventions.”

The study findings indicated that among younger patients, those with colorectal cancer had higher lactate levels and more Veillonella parvula, a gut bacterium that feeds on lactate. Tumors can produce high levels of lactate, which V. parvula uses to grow. Whether that relationship plays a role in early-onset disease is not yet known.

Early-onset (EO) breast cancer showed changes across 64 bacterial species and lower levels of primary bile acids. In breast cancer, one of the 64 species that differed in younger patients was Clostridium scindens, a bacterium involved in bile acid and steroid metabolism.

Colorectal and breast cancer rates are rising among younger adults, the authors stated. Colorectal cancer incidence is increasing about three percent a year among adults ages 20 years to 49 years, while breast cancer incidence is rising 1.4% a year among women younger than 50 years, according to the American Cancer Society. And while the colorectal and breast cancer findings do not establish that these microbial or metabolic differences cause early-onset disease, but they identify links that warrant further study. No comparable age-related microbiome differences were found in brain cancer, the third cancer examined in the early-onset analysis.

Researchers identified gut bacteria associated with survival in colorectal, liver and intrahepatic bile duct, ovarian and prostate cancers, and melanoma. In liver and intrahepatic bile duct cancer, Bifidobacterium longum was associated with longer survival and Blautia A massiliensis with shorter survival.

Researchers also studied whether the gut microbiome before treatment was associated with diarrhea during chemotherapy, a side effect that can make treatment harder to tolerate. Among patients receiving 5-fluorouracil, or 5-FU, a chemotherapy used to treat many types of cancer, those who later developed diarrhea had lower levels of bacterial genes capable of breaking down the drug. Much of that function came from Anaerostipes hadrus, a common gut bacterium. “This example underscores the potential of leveraging our real-world mixed-cancer, mixed-treatment cohort to identify microbiome-driven mechanisms underlying cancer treatment-related adverse effects,” they wrote. The same signal was not linked to diarrhea in patients receiving carboplatin, another chemotherapy drug, suggesting the finding was specific to 5-FU.

“The microbiome is not the sole driver of cancer or treatment outcomes, but it is an underappreciated component that has not traditionally been considered in therapeutic approaches,” said Kashyap. “This gives us a proof of concept that we can begin to understand why some patients experience a particular side effect and identify a target that could potentially be acted upon.”

The researchers next aim to investigate whether cancer-specific microbial signals play a causal role in disease and validate the microbiome’s potential to predict treatment side effects in larger patient groups. In their paper the team concluded, “Our findings illustrate how MCCM, a large, real-world mixed-cancer, mixed-treatment cohort, complements traditional case-control designs by more precisely identifying microbial contributions to cancer pathogenesis, EO cancer, and treatment-related adverse events … These findings demonstrate the strength of our cohort and provide a foundational resource for the discovery of cancer-specific microbiome signatures and predictive biomarkers.”

The post Microbiome Patterns Vary Among Individuals with Different Cancer Types and Onset Age appeared first on GEN - Genetic Engineering and Biotechnology News.

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Panelists:

Ali Strtak, PhD

Product Manager, Organoids
Bio-Techne

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Ali Strtak, PhD

Ali Strtak, PhD, is product manager for organoids at Bio-Techne. Ali earned her PhD studying the mechanisms of enteric viral infections, using intestinal organoid models to understand how nonstructural viral proteins co-opt host pathways and boost replication, and how that, in turn, translates to the physical manifestations of disease. She published the first functional characterization of a virally encoded calcium ion channel in the Caliciviridae family. Optimizing culture conditions as well as calcium imaging protocols for that work gave her firsthand experience with how culture variability and reagent selection underpin and undermine reproducibility in organoid models. In her current role, she focuses on standardizing organoid culture to make the model more consistent experiment over experiment and more accessible to all researchers interested in getting into organoids, regardless of prior 3D culture expertise.

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Fikri Birey, PhD

Assistant Professor, Department of Human Genetics
Emory University School of Medicine

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Fikri Birey, PhD

Fikri Birey, PhD, is an assistant professor in the Department of Human Genetics at Emory University School of Medicine, where he leads a research program focused on uncovering the molecular and cellular mechanisms of human brain development and neurodevelopmental disorders. His lab employs stem cell-derived brain organoids and assembloids to model disease-relevant processes, with particular emphasis on disorders such as autism, epilepsy, and schizophrenia. Birey completed his PhD in genetics at Stony Brook University and postdoctoral research at Stanford University in the laboratory of Sergiu Pasca, MD, where he built the first assembloid platform and applied it to uncover previously inaccessible disease phenotypes and nominate novel therapeutics in Timothy syndrome. He also co-founded the Brain Organoid Hub at Emory, which serves as a central resource for scalable and standardized human brain organoid research. Through this work, Birey aims to bridge basic neurobiology with therapeutic discovery, advancing precision medicine for complex brain disorders.

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Complex biologics such as bifunctional antibodies are opening new therapeutic possibilities in oncology, but these molecules present significant challenges for manufacturing teams. Non-standard architectures can often translate to low expression and difficult developability, making cell line development a critical bottleneck between a promising sequence and a viable clinical candidate.

In this GEN webinar, Joseph Shultz (vice president of technical development and manufacturing, Ottimo Pharma) and Imroz Ghangas (vice president of commercial sales, Asimov) discuss strategies for achieving high-performing clonal titers and advancing a dual-paratopic cancer immunotherapy from sequence to dosed patient in under a year. Attendees will learn about the unique attributes of Ottimo’s molecule and how a specialist partnership with Asimov accelerated the program. The presenters will also introduce the CHO Edge System, which combines Asimov’s proprietary GS knock-out CHO host, hyperactive transposase, library of characterized genetic elements, and AI-driven genetic design tools to routinely deliver clonal titers of 8-12 g/L.

A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelists.

Produced with support from:

The post Advancing Brain Organoids from Research Models to Scalable Platforms appeared first on GEN - Genetic Engineering and Biotechnology News.

The Boston study raises the interesting prospect of an accessible new target for therapeutic development. The paper, published today in Nature, is entitled: “Human genetics implicates a BACH2-NRF2 axis in fetal hemoglobin activation.”

These new findings “establish the BACH2–NRF2 axis as a tractable and potentially therapeutically targetable regulatory node involved in HbF activation,” the authors write.

For the past few decades, researchers have focused on the fetal-to-adult hemoglobin switch as a potential therapeutic avenue for SCD and thalassemia. Fetal hemoglobin expression declines naturally in the first 6-12 months after birth, replaced by adult hemoglobin. Almost 20 years ago, teams led by Swee-Lay Thein, MD, and, separately, Sankaran and Stuart Orkin, MD, identified BCL11A as a key regulator of that switch. The approval in December 2023 of Casgevy, the gene editing therapy sponsored by Vertex and CRISPR Therapeutics, provided clinical validation of that strategy and has transformed the lives of scores of SCD and thalassemia patients.

In the Nature report, Sankaran’s team analyzed a trove of genome-wide association study (GWAS) data from more than 28,000 individuals spread across European, African, and Asian populations. The study identified 91 discrete genetic associations across 12 genomic regions. One of the strongest signals, albeit weaker than the original GWAS findings two decades ago, highlighted a novel regulatory circuit—the BACH2–NRF2 axis—that directly governs γ-globin gene expression.

BACH2 variations

BACH2 is a known transcription regulator, Sankaran told GEN, but it was not previously suspected as having a role in HbF regulation. Sankaran’s team performed studies to pinpoint the precise genetic variant that contributed to the GWAS signal. The causal variant—rs1010474-C—reduces expression of BACH2 in erythroid progenitor cells. Genetic and biochemical experiments to block BACH2, either using short hairpin RNA knockdown, base editing, or pharmacological inhibition using a small-molecule inhibitor, led to marked elevation of γ-globin transcription (one of the two globin chains that make up HbF) and increased the proportion of HbF-containing red blood cells without disrupting normal erythropoiesis.

Sankaran’s team went on to demonstrate that BACH2 functions as a direct repressor at the γ-globin promoter and locus control region LCR. Under baseline conditions, BACH2 restricts chromatin occupancy of the transcriptional activator, NRF2. But if BACH2 is lost or inhibited, NRF2 binding is able to expand across γ-globin regulatory elements. Loss of BACH2 triggers the formation of discrete nuclear NRF2 foci that specifically colocalize with active sites of γ-globin transcription.

By mapping the transcription factor binding sites, the team identified overlapping consensus motifs for BACH2 (−94 to −106) and NRF2 (−96 to −105) within the upstream γ-globin promoter. Using base editors, the team engineered single-nucleotide substitutions to study the impact of targeted point mutations on gene expression. Promoter variants including −98G>A, −99G>A, and −104G>A—similar to those that might be contemplated in a therapeutic setting—reduced BACH2 binding affinity while enhancing NRF2 binding, resulting in robust HbF expression. Biochemical analysis further confirmed a direct protein interaction between domains of BACH2 and NRF2, indicating that BACH2 physically interacts with NRF2 to mute its transcriptional activity.

Parallel pathways

The Nature study from Sankaran’s team also shows that the BACH2–NRF2 axis operates independently of BCL11A. The BACH2–NRF2 promoter motif is sandwiched between two BCL11A binding sites. The researchers found no evidence of direct physical contact between BCL11A and BACH2 or NRF2. Furthermore, simultaneous depletion of both BACH2 and BCL11A yielded additive increases in γ-globin expression, suggesting the potential for multi-target genetic or pharmacological therapies.

Sankaran tells GEN he is excited by the finding that the BACH2 pathway is “completely independent of the BCL11A repressive pathway and is primarily involved in activation of HbF. So, combined editing at the [gamma-globin] promoters,” in addition to what companies like Shanghai-based CorrectSequence Therapeutics is doing at the BCL11A binding site, “could also be beneficial.”

Addressing the translational potential of their work, Sankaran and colleagues emphasize that “the presence of high-confidence human genetic evidence is a more critical predictor of clinical success than the absolute magnitude of the variant effect size.”

Naturally, this report raises the intriguing prospect of new avenues for combining BCL11A-targeted strategies with BACH2/NRF2 modulation for treating SCD and β-thalassemia. “There are already small molecules in development for SCD that we suspect might target BACH2,” Sankaran said. “I think our findings add clarity on the mechanism by which this pathway might modulate HbF.”

The post Genome-Wide Analysis Identifies BACH2 as Potential Fetal Hemoglobin Activation Target appeared first on GEN - Genetic Engineering and Biotechnology News.

S. aureus is one of the most concerning bacterial pathogens, given that MRSA accounts for the largest increase in the global antimicrobial resistance burden. In addition, deaths attributable to S. aureus infections have doubled since 1990, making it a leading cause of bacterial mortality worldwide. Despite the continued focus on research, tissue reservoirs that permit bacterial persistence remain poorly defined.

Now, a new study reveals how MRSA exploits the osmotic environment of the inner kidneys to establish a bacterial reservoir and hide from the immune system. This work suggests that MRSA can establish niches in the kidneys and the findings provide a mechanistic explanation for a longstanding question in the field of MRSA biology, and could inform future strategies aimed at limiting kidney damage from infections.

This work is published in Science Translational Medicine in the paper, “Hyperosmotic niche adaptation and tissue polyamines underlie MRSA persistence in the kidney.”

Nobuhiro Kanazawa, PhD, and colleagues used intravenous MRSA infection in mice and combined with multi-plexed imaging, dual-species transcriptomics, host and bacterial genetics, and cell-­based assays, to understand the mechanisms of MRSA persistence in the kidney in a mouse model of systemic infection. The findings reveal the renal inner medulla, the site of urine concentration, as an MRSA reservoir. Here, in this hyperosmotic niche, MRSA evaded immune detection and co-opted tissue polyamines to grow and spread toward the renal cortex.

MRSA spread to other kidney tissues and grew by co-opting polyamines, which buttressed the bacterial membrane against osmotic stress and boosted the translation of a growth-fueling bacterial enzyme.

The extreme osmotic environment also shielded MRSA from immune detection and slowed the migration of neutrophils toward the infection site. More specifically, neutrophil recruitment to the inner medulla was delayed.

The team went on to find that the approved drug furosemide restored neutrophil infiltration and contained MRSA’s spread in the kidneys of mice, hinting that similar “washout” therapies might prove useful. The authors write, “disruption of medullary osmolality with the loop diuretic furosemide accelerated neutrophil infiltration, limited bacterial spread, and improved renal outcomes.”

The findings, the authors note, revealed the inner medulla as a physiologically immune-­restricted MRSA reservoir and supported “modulation of medullary osmolality and bacterial polyamine metabolism as candidate adjunctive strategies for limiting renal persistence and dissemination during MRSA bacteremia.”

The post MRSA Exploits Kidney’s Inner Environment to Persist and Spread appeared first on GEN - Genetic Engineering and Biotechnology News.

The Baylor College of Medicine-led study, “Leveraging high-throughput proteomics and AI-based protein folding to accelerate VAV1 molecular glue discovery,” was published in Nature Communications. The team was led by senior and co-corresponding author Jin Wang, PhD, director of Baylor’s Center for NextGen Therapeutics, and first and co-corresponding author Hanfeng Lin, PhD, a postdoctoral researcher in Wang’s laboratory.

“Many scientists are increasingly exploring a new way to treat disease: instead of blocking harmful proteins, they aim at eliminating them entirely,” Wang said. Because degradation via molecular glue removes the whole protein rather than inhibiting one of its functions, the strategy could produce a more complete therapeutic effect.

“To find compounds capable of degrading VAV1, we screened a library of molecules using high-throughput proteomics, a technology that can assess thousands of proteins simultaneously. This unbiased analysis revealed a series of compounds, including NGT-201-12, that caused VAV1 levels to drop while affecting relatively few other proteins,” added Lin. Follow-up studies showed that degradation depended on the proteasome and cereblon (CRBN), a component of the cell’s protein-degradation pathway.

The team then developed GluePlex, a computational workflow that integrates AI-based protein-structure prediction with physics-based modeling. Without relying on an experimental structure of the ternary complex, GluePlex modeled how VAV1, CRBN, and the molecular glue assemble. “The model identified a specific region of VAV1, known as the SH3-2 domain, as being essential for degradation. Experimental tests confirmed the prediction and pinpointed the exact spot the glue uses: a small surface loop on VAV1 that acts as a degradation signal, or ‘degron.’ This loop is different from degradation signals commonly associated with cereblon-targeting molecular glues,” Lin said.

“Applying Free Energy Perturbation (FEP) to predicted ternary structures yields cooperativity metrics that correlate with degradation potency, overcoming limitations of standard docking and enabling prospective ranking of analogs—even from weak initial binders,” the authors wrote. Adding halogen substitutions restricted molecular flexibility and improved degradation efficiency, producing NGT-201-18, a more potent degrader that formed a stronger degradation complex. In primary human T cells, NGT-201-18 reduced VAV1 levels and suppressed T-cell activation. Dose-response proteomics identified VAV1 as the principal target but also revealed degradation of LIMD1, an off-target carrying a canonical G-loop degron. The finding shows that one molecular glue can engage structurally distinct degrons and underscores the importance of proteome-wide profiling.

The compounds remain preclinical, and additional studies will be needed to assess their pharmacology, safety, selectivity, and activity in disease models. Still, the work offers both a starting point for therapies aimed at VAV1-driven autoimmune disorders and hematologic malignancies and a broader discovery strategy. “This work introduces a series of VAV1-targeting molecular glues and, just as importantly, shows how artificial intelligence, structural modeling and proteomics can work together at the earliest stage of a project,” Wang said.

The post AI and Proteomics Accelerate VAV1 Molecular Glue Discovery appeared first on GEN - Genetic Engineering and Biotechnology News.

SPR2015 is a preclinical molecular glue, more specifically an oral KRAS G12D (ON) inhibitor that SciBrunch is developing for forms of cancer that include colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic ductal adenocarcinoma (PDAC)—the most common and aggressive type of pancreatic cancer.

KRAS G12D is the most common oncogenic RAS mutation in human tumors—with a 38% prevalence in pancreatic cancer, CRC, and NSCLC, according to a 2023 study. The mutation results from a substitution of glycine with aspartate at position 12, a change that leaves KRAS active and continuously signaling for cell proliferation and survival, SciBrunch said.

According to SciBrunch, SPR2015 has shown nanomolar antiproliferative activities in various KRAS G12D-mutant cell lines while maintaining good selectivity over KRAS wildtype cells.

At the 2026 American Association for Cancer Research (AACR) Annual Meeting, a team of SciBrunch researchers that included founder, chairman, and CEO Tao Hu, PhD, presented preclinical data showing SPR2015 to have demonstrated what it termed compelling antitumor efficacy as a monotherapy across multiple in vivo cell-derived and patient-derived xenograft (CDX and PDX) models.

“SPR2015 is a highly potent and selective KRAS G12D (on) inhibitor with nanomolar proliferation inhibitory activities in various KRAS G12D cell lines while with good selectivity over KRAS wild type,” Hu and SciBrunch researcher colleagues reported in a poster presentation during AACR 2026. They added that PR2015 was expected at the time to human Phase I studies by the end of this year.

In a head-to-head mouse study comparing a single oral once-daily dose at 100 mg/kg of SPR2015 to another unspecified G12D (ON) inhibitor in over 15 CRC CDX or PDX models, SPR2015 showed significantly superior efficacy in the in vivo CRC xenograft models, achieving a 64.7% objective response rate (ORR) and 94.1% disease control rate (DCR) as monotherapy.

“The diligence question is whether those properties survive translation into humans strongly enough to compensate for SPR2015’s later start,” Sreyashi Paul, PhD, business analyst with Lucidquest Ventures, commented on the firm’s website.

Paul cited the 52% confirmed ORR and 93% disease control rate of Revolution Medicines’ zoldonrasib (RMC-9805) in 27 efficacy-evaluable previously treated KRAS G12D NSCLC patients, reported in May, as well as the early human clinical data produced by Verastem’s VS-7375 in the Phase I/II TARGET-D 101 dose escalation and dose expansion trial (NCT07020221). In June, Verastem reported Phase I/II trial (NCT06162221) data showing 93% (13/14) of heavily pretreated (second- to fourth-line) patients with metastatic PDAC who received 900 mg once-daily monotherapy achieved greater than 50% reduction in the tumor marker CA19-9.

In their announcement, Merck and SciBrunch did not disclose a current timeframe for taking SPR2015 into Phase I.

“Validates R&D strength”

“This agreement with Merck not only validates the R&D strength of our platform but also underscores the potential of SPR2015 in addressing longstanding unmet medical needs in oncology,” Hu said in the companies’ statement. “We are excited that Merck, a global leader in oncology, will take SPR2015 forward.”

Merck agreed to pay SciBrunch up to $2.13 billion consisting of $400 million upfront and the remainder in payments tied to achieving development, commercialization, and other milestones across multiple indications.

Merck will record a pre-tax charge of $400 million related to the SciBrunch agreement, or approximately $0.13 per share, to be included in its GAAP and non-GAAP results for the third quarter. The transaction has closed.

“Evidence continues to accumulate for the therapeutic potential of targeting the KRAS pathway, a well-characterized factor in tumor cell growth,” stated George Addona, senior vice president, discovery, preclinical development and translational medicine, Merck Research Laboratories. “This agreement complements and diversifies our expanding pipeline of precision targeted candidates with SPR2015, a potent engineered inhibitor for one of the most prevalent mutant forms of KRAS found in human cancers.”

The deal continues the trend of U.S. and other Western pharmas partnering with Chinese biotechs on drug development—and in Merck’s case, a trend of striving to rebuild its cancer pipeline in hopes of recouping sales that it stands to lose when its anchor drug, the multi-indication cancer immunotherapy Keytruda® (pembrolizumab), loses exclusivity for key U.S. patents in 2028.

Keytruda generated $15.81 billion in Q1–Q2 2026 sales in addition to the $31.641 billion it generated last year. Those figures do not include the $590 million racked up by Keytruda Qlex, a subcutaneous injection form of Keytruda that won FDA approval in September 2025. A consensus of Wall Street analysts has forecast peak annual revenue for Keytruda of approximately $33 billion by 2028.

$70B potential opportunity

However, Merck envisions more than making up for the loss of Keytruda, having foreseen more than $70 ​billion of potential ⁠commercial opportunity by the mid-2030s, Louise Chen, a managing director with Scotiabank, told Reuters.

Founded in 2014, Shanghai-based SciBrunch focuses on small molecule oncology therapeutics based on clinically validated targets and differentiated product design strategies. Hu, a serial entrepreneur, founded SciBrunch with medicinal chemist Yang Zhang, PhD, who is the company’s CSO.

In January, SciBrunch completed an oversubscribed Pre-A round financing of over $35 million, bringing its total capital raised to $65 million over two rounds. Among intended uses for the proceeds, the company announced at the time, was “advancing IND-enabling studies for a new generation of innovative molecular glue RAS inhibitors, exploring their clinical potential in RAS-mutated refractory tumors including colorectal cancer, pancreatic cancer, and non-small cell lung cancer, with the goal of developing preferred therapies for RAS-driven cancers.”

HighLight Capital led the $35 million Pre-A round, with participation from new investor InnoPinnacle Fund and existing shareholders that increased their investments in SciBrunch, including Hankang Capital, BioTrack Capital, LongRiver Investments, and Elikon Venture.

“Since our founding, SciBrunch has remained focused on advancing innovative therapies targeting the RAS pathway and is committed to delivering transformative treatment options for patients with pancreatic, colorectal, lung, and other major malignant tumors,” Hu added.

SPR2015 is not SciBrunch’s lead candidate. That distinction belongs to SPR1020, a brain-penetrant PARP1 selective inhibitor being developed to fight metastatic brain cancer (mBC, with or without brain metastases), ovarian cancer, PDAC, prostate cancer, and glioblastoma. SPR1020 is under study in patients with advanced solid tumors in a Phase I/II open-label, first-in-human trial (NCT07359066)  which dosed its first patient on January 8.

“SPR1020 is expected to demonstrate significant efficacy against tumors harboring BRCA mutations or homologous recombination repair (HRR) pathway gene alterations (e.g., breast cancer, prostate cancer),” SciBrunch predicted in the trial’s page on ClinicalTrials,gov.

The post Merck, SciBrunch Launch Up-to-$2.13B Collaboration to Develop Preclinical KRAS-Inhibiting Molecular Glue appeared first on GEN - Genetic Engineering and Biotechnology News.

Yet despite its clinical success, manufacturing remains a fundamental bottleneck to broader patient access.

The challenge facing CAR T is no longer clinical validation; it is scalable delivery. Manufacturing remains constrained by donor-to-donor variability, patient-specific production, and complex multi-step workflows operating within tightly controlled GMP environments.^3,4 These factors drive up cost, increase process variability, and limit manufacturing throughput, ultimately restricting patient access to potentially life-saving therapies.

In addition, existing analytical approaches were either never designed to work in real time or have limited capacity to predict manufacturing outcomes. Most inline sensors or probes rely on downstream or metabolite-based measurements that describe what a cell has done, rather than what a cell can become. This limits process visibility and reduces opportunities for informed intervention before failure occurs.⁵

As the field moves toward larger patient populations and commercial-scale manufacturing, the industry faces a critical challenge: how do we move from reactive manufacturing to predictive control? Solving this challenge is essential to improve manufacturing robustness, reduce the cost of goods, increase manufacturing capacity, and expand patient access to advanced cell therapies.

Achieving these goals will require more than automation alone. It will need technologies capable of revealing cellular states earlier in the manufacturing process, enabling informed intervention, and a transition from retrospective testing to proactive process control.⁵

To address this challenge, Cytomos has developed AuraCyt^®, a predictive cell intelligence platform designed to reveal cellular states earlier in the manufacturing process and support more informed manufacturing decisions.

From dielectric signatures to predictive cell intelligence

Cells carry rich biophysical information that is not always visible through conventional biological markers. Dielectric spectroscopy accesses this information by measuring the frequency-dependent electrical behavior that arises from a cell’s intrinsic structure.^6-9

Specifically, the cell membrane separates the conductive interior of the cell from its surrounding environment, shaping how the cell responds to an applied electric field. As the frequency increases, the influence of the cell membrane decreases, allowing the electrical response to become progressively more sensitive to intracellular structure and composition as well as membrane properties.^6,8,9 The resulting electrical response reflects the intrinsic physical state of the cell.

AuraCyt captures this response at the single-cell level using ultra-wideband dielectric spectroscopy. By measuring each cell across more than 200 frequencies, the platform generates a high-dimensional digital fingerprint of every cell that reflects the cellular state and captures subtle changes associated with emerging behavior. In the current configuration, this produces 507 parameters per cell, generating biologically grounded, AI-ready digital datasets for cell characterization and predictive analysis.¹⁰

This approach represents a paradigm shift in cell analytics: using physics to predict biology. As changes in cellular state often precede measurable biological outcomes, AuraCyt signatures can reveal early signals and emerging cellular trajectories before they are detected by conventional assays. This provides a biophysics-first route to predictive cell intelligence.^5,10

Applying predictive cell intelligence to CAR T manufacturing

To demonstrate how predictive cell intelligence can be applied in a real manufacturing workflow, AuraCyt was evaluated in a CAR T manufacturing case study focused on transduction efficiency and process risk.

Transduction efficiency is a critical determinant of the CAR T manufacturing success, yet current analytical methods typically confirm transduction only after key manufacturing decisions have been made. Cytomos decided to investigate whether predictive cell intelligence could provide earlier insights into manufacturing outcomes.

AuraCyt was evaluated as a rapid, label-free platform for monitoring transduction efficiency and characterizing transduced and non-transduced T-cell populations over an eight-day manufacturing workflow.

Donor-derived T cells were activated with IL-2 and expanded using a standard CAR T manufacturing process. Following activation, the cell population was divided into two arms: one transduced with a CD34-CAR construct and a matched non-transduced control.

AuraCyt analysis was performed on Days 0, 4, 6, and 8. Flow cytometry was performed on Day 6 to confirm CAR-CD34 expression, providing a conventional benchmark for transduction assessment against which earlier AuraCyt measurements could be compared. Cell viability and concentration were monitored throughout the process (Figure 1).

Using Day 0 donor T cells as a reference population, AuraCyt tracked the evolution of both transduced and non-transduced cells over time. Comparison of the resulting dielectric signatures using effect size analysis demonstrated divergence between the two populations by Day 4, prior to conventional confirmation of CAR expression by flow cytometry on Day 6 (Figure 3).

Implications for CAR T manufacturing and beyond

These findings demonstrate how early AuraCyt signatures can reveal CAR T manufacturing trajectories before conventional assessment. By providing earlier insight into cellular states, AuraCyt has the potential to move manufacturing from retrospective quality control towards predictive process control.

Earlier visibility of process trajectory could improve manufacturing consistency, reduce variability, and support more informed decision-making during critical manufacturing windows. In turn, this may help lower the cost and complexity of delivering advanced cell therapies at scale.

Beyond CAR T, the same biophysics-first approach could be applied across cell therapy, biologics, and other advanced manufacturing workflows, providing a foundation for predictive biomanufacturing and AI-enabled process optimization.

Lindsay Fraser, PhD, is CSO at Cytomos.

References

1. U.S. Food and Drug Administration (FDA). Approved Cellular and Gene Therapy Products. Center for Biologics Evaluation and Research, FDA.

2. MarketsandMarkets. CAR T-Cell Therapy Market Report 2026–2031.

3. Ayala Ceja M, Khericha M, Harris CM, Puig-Saus C, Chen YY. CAR T Cell Manufacturing: Major Process Parameters and Next-Generation Strategies. Journal of Experimental Medicine. 2024.

4. Baguet C, Larghero J, Mebarki M. Early Predictive Factors of Failure in Autologous CAR T-Cell Manufacturing and/or Efficacy in Hematologic Malignancies. Blood Advances. 2024.

5. Mendoza R, Carter K, Peterson S. Early-stage Analytical Development Strategies for Cell Therapy. Cell & Gene Therapy Insights. 2024;10(11):1493–1503.

6. Gawad S, Schild L, Renaud P. Micromachined Impedance Spectroscopy Flow Cytometer for Cell Analysis and Particle Sizing. Lab on a Chip. 2001.

7. Cheung K, Gawad S, Renaud P. Impedance Spectroscopy Flow Cytometry: On-Chip Label-Free Cell Differentiation. Cytometry Part A. 2005.

8. Liang W, Zhao Y, Liu L, et al. Determination of Cell Membrane Capacitance and Conductance via Optically Induced Electrokinetics. Biophysical Journal. 2017.

9. Tehrani FD, O’Toole MD, Collins DJ. Tutorial on Impedance and Dielectric Spectroscopy for Single-Cell Characterisation on Microfluidic Platforms: Theory, Practice, and Recent Advances. Lab on a Chip. 2025.

10. Fraser L, Wright D, Hunter B, Giakoumelou S, Bellot F, et al. Biology Empowering AI: Rethinking Prediction in Biomanufacturing. Poster presented at the International Society of Cell & Gene Therapy (ISCT) Annual Meeting, Dublin, Ireland; 6–9 May 2026. Supported by the attached ISCT poster.

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The study “UHRF1 overexpression generates senescent states with different T53 dependencies,” published in EMBO Reports, found that the gene can trigger several forms of cellular senescence, a natural defense in which damaged cells stop dividing to help prevent cancer, a tumor-suppressive function inherent to all cells.

Using a zebrafish model of liver cancer, the researchers investigated the initial response to a cancer-causing gene and found that some of these precancerous cells are terminally senescent, meaning they cannot generate tumors, while others can regain the ability to divide and potentially contribute to cancer.

Commonly used chemotherapies frequently cause cancer cells to enter senescence, but do not fully eliminate these cells. Therefore, it is useful to target these therapy-induced senescent cells with senolytics that eliminate them, say the researchers.

In this study, the team tested a common senolytic to investigate its ability to target senescent cells and found that it was effective against only some of the precancerous cells but not others. The findings suggest that treatments targeting senescent cells may need to account for the different ways these cells behave.

“Cancer is not simply a matter of whether a cell stops dividing or continues to grow. Our study shows that there are different types of cellular senescence, and depending on the type acquired by a pre-cancerous cell, the outcome can make the difference between turning into a cancer cell or not,” explained Professor of Biology at NYU Abu Dhabi and senior author Kirsten Sadler Edepli, PhD.

“We also show that these different forms of senescent cells have hugely different responses to treatments, which is important when developing and applying cancer therapies. It is particularly exciting that our undergraduate capstone researchers contributed to this discovery. Their work demonstrates the valuable role students can play in high-impact research when they are given the opportunity to engage directly with important scientific questions and are given dedicated mentors to guide their efforts.”

The research was conducted by NYU Abu Dhabi researchers in collaboration with the University’s Center for Genomics and Systems Biology. The findings provide new insight into how cells respond when cancer-causing genes are activated and could help researchers better understand how different types of senescent cells should be targeted in cancer treatment, according to the investigators.

The post How Cells Respond Differently to a Cancer-Causing Gene appeared first on GEN - Genetic Engineering and Biotechnology News.

The founding members listed in today’s announcement include AbbVie, argenx, Lundbeck, and Takeda, and the consortium remains open to additional pharma and biotech companies interested in joining. Under the terms of the consortium, each founding member will contribute proprietary antibody sequencing with Gingko Datapoints, an offering of Gingko Bioworks, filling any remaining capacity from publicly available sources. The goal is to reach 10,000 antibodies in total.

“This consortium represents an important step forward in building predictive models for antibody developability by creating datasets that are designed for machine learning, addressing limitations associated with convenience datasets,” said Athena Hadjixenofontos, PhD, director of data science, head of AI in biotherapeutics and genetic medicine at AbbVie. “Federated infrastructure enables participants to contribute data while keeping proprietary sequences private. These capabilities could meaningfully accelerate antibody discovery and help advance new medicines for patients.” 

Antibody developability encompasses the biophysical properties that influence whether a candidate antibody can be manufactured, formulated, and successfully advanced into a clinical product. Predicting barriers that could prevent promising antibody candidates from progressing early could support more informed candidate selection and reduce development time and investment.

This is important, for example, “in complex therapeutic areas such as CNS” where “the ability to select well behaved candidates with superior developability properties is essential,” said Allan Jensen, PhD, vice president, biotherapeutic discovery at Lundbeck. “By bringing together diverse antibody dataset[s], this collaboration has the potential to strengthen predictive approaches.”

According to the partners, Gingko Datapoints is leading the scientific design and execution of the consortium. This includes designing the sequence selection approach, overseeing antibody production, and conducting high-throughput wet-lab characterization across core developability endpoints. Gingko is also training a foundation antibody developability model on the dataset in Apheris’ secure environment. 

For its part, Apheris’ federated infrastructure is being used to deliver the foundation model into each participating member’s environment where they can fine-tune it on their proprietary data. Furthermore, members will be able to train, benchmark, and refine their own internal models in Apheris’ environment using the full consortium dataset as well as their own sequence data, without exposing their proprietary information to other members. The consortium has also tapped Charlotte Deane, PhD, professor of structural bioinformatics at the University of Oxford and Peter Tessier, PhD, professor of pharmaceutical sciences and chemical engineering at the University of Michigan, to provide independent scientific oversight.

Members are expected to have access to the initial dataset by early 2027. There are also plans to explore the addition of more complex antibody formats over time to enable new drug classes and other key properties that help the members predict which drugs will succeed or fail. 

“Pooling standardized developability data across the industry can create stronger predictive models than any one company could build alone,” said Yves Fomekong Nanfack, PhD, head of AI/ML research at Takeda. “As we advance Takeda Research’s ambition to become an AI-native discovery organization, this capability can help identify promising antibody candidates earlier, inform better development decisions, and bring new therapies to patients faster.”

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The study, “Monoallelic variants in BRSK1 are associated with a neurodevelopmental disorder with or without epilepsy,” was led by researchers at Baylor College of Medicine, the Duncan Neurological Research Institute at Texas Children’s Hospital, and the Texome Project, together with collaborating institutions. It was published in the American Journal of Human Genetics.

According to Hugo Bellen, PhD, who is co-lead author of the study, the work began with a child enrolled in the Texome Project, which provides genetic testing to medically underserved people with rare, undiagnosed conditions in Texas. Standard analysis of the child’s and parent’s genomes had not identified a cause. AI-MARRVEL, an artificial intelligence–based tool that analyzes genomic and clinical information to prioritize candidate disease variants, highlighted a rare change in BRSK1. Through GeneMatcher, the researchers identified nine additional affected individuals with rare heterozygous variants in the gene, bringing the group to 10 people from seven unrelated families. The team then modeled three patient-derived variants in Drosophila melanogaster to test their effects in a living organism.

The “affected individuals present with developmental delay and variable phenotypes including anxiety, attention-deficit hyperactivity disorder (ADHD), autism, and seizures,” the authors wrote, adding that the severity and symptoms varied. Symptoms differed even among relatives carrying the same variant, suggesting variable expressivity.

“We studied the fly equivalent of BRSK1, called sff (sugar-free frosting), and found that this gene is active primarily in neurons, mirroring the expression pattern seen in humans,” added Mingxi Deng, PhD, who is first author and a postdoctoral fellow in the Bellen lab. “When the fly gene was disabled, the flies developed difficulties moving, showed increased sensitivity to stressors that can trigger seizure-like behavior, became more vulnerable to heat-induced paralysis and lived shorter lives. These findings indicated that the gene is essential for normal nervous system function.”

Introducing normal human BRSK1 largely corrected the behavioral and neurological defects, whereas three variants (BRSK1^p.Ile202Val, BRSK1^p.Arg237Cys, and BRSK1^p.Thr406Ile) found in affected individuals produced only a partial rescue. The patient variants also failed to normalize neuromuscular junction structure or levels of Futsch, a protein involved in organizing neuronal microtubules. Together, the experiments suggest that the variants partially reduce BRSK1 activity rather than eliminating it.

“Microtubule disruption has been linked to several neurodevelopmental and neurological disorders,” Deng said. “Our findings suggest that reduced BRSK1 function interferes with the cellular machinery needed for healthy brain development and communication between neurons.”

BRSK1 encodes a kinase involved in neuronal polarization, synaptic function, and the internal organization of nerve cells. Reduced activity may therefore interfere with the cellular machinery neurons need to develop and communicate. “This work improves our understanding of the genetic causes of neurodevelopmental disorders and highlights the power of combining AI-driven gene discovery with experimental studies in model organisms to uncover new rare diseases and their underlying biology,” Bellen said.

The diagnosis may help participating families understand the source of their condition and could guide recognition of additional cases. Future studies will be needed to determine why the same variant can produce markedly different symptoms and to define more precisely how altered BRSK1 activity affects the developing brain.

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The treated mice kept roughly 40% more tissue in memory centers of the brain and did better on a memory test compared with untreated mice—even though the levels of tau in their brains didn’t change. “In tauopathies, including Alzheimer’s disease, there’s no treatment right now that actually decreases neurodegeneration,” said David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor in WashU Medicine’s Department of Neurology. “If we can show that we’re really decreasing brain cell death, it’s certainly worth trying to pursue that pathway to prevent the most devastating consequences of these diseases.”

Holtzman is senior author of the team’s published paper in Neuron, titled “Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy,” in which they concluded “Our study defines the CXCR3 axis as a critical target that, when blocked, mitigates CD4+ and CD8+ T cell infiltration and confers neuroprotection in a model of tau-mediated neurodegeneration in vivo without influencing levels of soluble or insoluble tau.”

There is no treatment available today to stop the death of brain cells in tauopathies—including Alzheimer’s disease—in which twisted clumps of a protein called tau accumulate in the brain. Cells near those clumps begin to die after tau accumulates, but growing evidence suggests that much of the damage doesn’t come from the protein directly. Instead, it’s the immune system’s response to tau that’s to blame for the damage that eventually robs people of their memory and independence.

The two existing Alzheimer’s drugs on the market—lecanemab and donanemab—target amyloid protein, which forms plaques between brain cells in the early stages of the disease, disrupts cell communication, triggers tau tangles to form inside neurons and eventually leads to cell death. These anti-amyloid medications can slow a person’s decline, but they haven’t been shown to keep brain cells from dying, and they don’t work against primary tauopathies—diseases marked by tau buildup in which amyloid never appears. Alzheimer’s is a secondary tauopathy in which both amyloid and tau proteins accumulate.

Earlier research led by the Holtzman lab raised the possibility that targeting T cells could be an alternative route to treating tauopathies, including Alzheimer’s. In a paper published in 2023 in Nature, Holtzman’s lab showed that in mice with tau buildup, T cells flood into the brain, especially in areas where tau is most abundant, and cause neurodegeneration. In a related paper published earlier this month in Nature Neuroscience, the team showed that those T cells get their instructions from lymph nodes outside the brain.

In their newly published paper the team noted, “Beyond the roles of reactive microglia and astrocytes, recent work has demonstrated an important role of T cells and adaptive immunity in tau-mediated neurodegeneration, as suggested in human brains with advanced tauopathy and demonstrated in transgenic models.”

How T cells got into the brain once activated remained unknown, however. “The signaling pathways driving brain T cell homing and infiltration in tauopathies remain unknown, and identifying and targeting mechanisms for the prevention of such entry may offer therapeutic potential,” the investigators added.

The cells are known to navigate by following chemical trails called chemokines, and Holtzman’s team had previously found that one chemokine—called CXCL10—was elevated in the tau-mouse model they were utilizing. Other groups had shown that CXCL10 was elevated in Alzheimer’s. Activated T cells carry a protein on their surface, CXCR3, that follows this particular trail. “We hypothesized that the CXCR3 axis is an important chemotactic gradient for brain-infiltrating T cells in tauopathy, thereby linking peripheral immune activation to tau-driven brain injury,” they stated.

For their latest reported study the researchers, including co-senior author Jason Ulrich, PhD, a professor of neurology at WashU Medicine, and first author Joshua T. Emmerson, PhD, a postdoctoral researcher in Holtzman’s lab, examined the brains of mice with tau accumulation, as happens in Alzheimer’s disease. They found that in mice that lacked the CXCL10 chemokine, or the receptor protein CXCR3 on T cells that binds to CXCL10, T cells did not infiltrate the brain, even when researchers deliberately provoked inflammation to elicit an immune response.

The team then injected an antibody that blocked CXCR3 into young mice that had tau buildup in their brains but hadn’t yet had major brain cell loss. Treatment was administered every five days for three and a half months. The results showed that compared with the untreated mice, treated animals had about half as many T cells in their brains at the end of treatment. The treated animals also preserved more brain tissue and exhibited less evidence of nerve cell damage. “In a mouse model of tauopathy and neurodegeneration, chronic systemic anti-CXCR3 treatment markedly reduced parenchymal CD4+ and CD8+ T cell accumulation, attenuated neurodegeneration, and improved aspects of cognition,” they noted.

Yet tau tangles appeared the same in treated and untreated animals. “A key point of interest was the rescue from neurodegeneration but no overt changes to tau pathology,” the researchers added.

Tests by Holtzman’s team also revealed that the antibody traveled to the border of each animal’s brain but not into the brain tissue—an important finding indicating that neurodegeneration can be treated without having to get a therapy into the brain itself.

“Our findings implicate a critical role of CD4+ T cells in accelerating tau-mediated neurodegeneration and suggest that peripheral CXCR3 inhibition could be a therapeutic approach in tauopathies,” the investigators said.

While more research is needed before the approach could be tested in people, Holtzman noted that existing drugs that target T cells—such as some therapies used for multiple sclerosis and other autoimmune disorders that occur when the body’s immune system attacks its own healthy cells—could be evaluated as Alzheimer’s therapies, opening a new therapeutic avenue for the disease.

“Tauopathies aren’t thought of as autoimmune disorders, so they haven’t been treated the same way, but this study shows for the first time in an animal model that these diseases respond to a specific T-cell therapy,” said Holtzman, who also directs WashU’s Hope Center for Neurological Disorders and the Knight Alzheimer Disease Research Center at WashU Medicine. “For this therapeutic approach, if it is safe, you wouldn’t have to design the drug to get into the brain—which is a big deal since most molecules don’t cross the blood-brain barrier well—and you don’t have to get rid of the tau to get this therapeutic effect.”

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The findings “Shield strike shatter in DNA topology and nuclease interactions,” which were published in Nature Communications, reveal how the structure of DNA influences its vulnerability to enzymatic breakdown.

According to the scientists, the study provides a dynamic view of a fundamental biological problem: why some DNA is accessible to enzymes while other DNA remains protected.

“Our high-speed AFM imaging allows us to follow the interaction between individual nuclease enzymes and DNA as it happens,” says student Jingge Yang. “We can see that DNA is not simply a passive target. Its local shape and higher-order organization strongly influence where enzymes interact and whether degradation can proceed,” adds Richard Wong, PhD, professor and team leader.

Watching DNA degradation molecule by molecule

DNA is constantly exposed to processes that can damage or break it. Some enzymes, nucleases, can deliberately break down DNA. They  play important roles in maintaining cells and clearing unwanted DNA.

One of the best-known of these enzymes is DNase I, which helps remove DNA released from damaged or dying cells. Problems with this clearance process have been associated with inflammatory and autoimmune diseases.

Although scientists know a great deal about the chemistry of DNase I, it has been difficult to see exactly how individual enzyme molecules approach DNA, where they remain and what happens immediately before and after the DNA is cut.

The HS-AFM movies revealed that DNase I did not interact with every part of a DNA molecule in the same way. The enzyme was frequently found near exposed DNA ends and regions where the DNA was curved or locally bent. Individual DNase I molecules could repeatedly return to restricted regions before visible fragmentation occurred.

Longer-lasting interactions were also more common around curved regions where DNA was more likely to be cut. Together, these observations showed that the shape of DNA influenced where the enzymes interacted with it.

Importantly, the HS-AFM cannot directly show the chemical reaction occurring at the enzyme’s active site. The researchers therefore describe the relationship between DNA shape, repeated enzyme engagement, and subsequent cleavage as a spatial and temporal correlation rather than direct observation of the catalytic reaction.

Five stages of DNA degradation

The researchers emphasize that STORM is a framework for describing the interaction patterns revealed by the experiments rather than a fixed sequence through which every enzyme molecule must pass.

The team also examined another DNA-cutting enzyme, micrococcal nuclease (MNase). Despite differences between DNase I and MNase, the team observed similar patterns of DNA sampling, localized interaction, repeated association, disruption and fragment redistribution. This suggests that STORM-like behavior may reflect broader physical principles governing how different nucleases interact with DNA.

The experiments also revealed how the physical organization of DNA can protect it from degradation. The researchers examined DNA condensed by protamine, a small protein that binds strongly to DNA. Protamines are particularly important in sperm cells, where they help package the paternal genome into an extremely compact form.

Under the experimental conditions, protamine caused DNA to form mainly two compact structures: elongated rod-like structures and ring-shaped structures called toroids. High-speed microscopy showed that DNase I molecules could gather around these condensed structures without destroying them. The toroidal structures were particularly compact. DNase I rarely penetrated their central regions, and the structures remained intact during continuous observation for more than six minutes despite the presence of the enzyme.

When the condensed structures were partially loosened, however, exposed regions again became susceptible to degradation. The results suggest that protection does not arise simply from the electrical interaction between protamine and DNA. Instead, tightly packing DNA into particular three-dimensional structures creates a physical barrier that limits the enzyme’s access.

Possible framework for understanding DNA protection and clearance

The findings could contribute to understanding how compact structures help preserve genetic information, including the exceptionally dense packaging found in sperm cells. They could also be relevant to extracellular DNA released from damaged or dying cells, which can stimulate immune responses if it is not efficiently removed.

The results may additionally be useful for the development of DNA-based therapeutics and gene-delivery systems. Packaging genetic material into structures that restrict nuclease access could potentially increase its resistance to degradation.

The post Scientists Observe Enzymes Breaking Down DNA in Real Time appeared first on GEN - Genetic Engineering and Biotechnology News.

Before we know it, they think to themselves, lives will be saved.

In the United States, such technology transfer is often taken for granted—but it hasn’t always been this way. As recently as 45 years ago, if the university researcher had gotten a grant from the federal government, then the federal government took ownership over what was invented.

This system stymied innovation. At the time, the federal government held the patents on roughly 28,000 discoveries, yet licensed fewer than 5% for commercialization. Something had to change.

And so, in 1980 Senator Birch Bayh (D-IN) and Senator Bob Dole (R-KS) drafted the Bayh-Dole Act of 1980 (Patent and Trademark Law Amendments Act, P.L. 96-517) to allow universities, small businesses, and non-profits to retain ownership and patent rights of inventions developed through research supported by federally funding—incentivizing the public-private collaborations required to transform scientific discoveries into new technologies, industries, products and companies.

The results have been a renaissance of innovation and licensing. The legislation’s ongoing success is highlighted in a new report by the Bayh-Dole Coalition, which includes the Biotechnology Innovation Organization (BIO) as a member. The 2026 report, “The Economic Impact of the Bayh-Dole Act,” provides impressive statistics.

Overall economic impact is enormous

In the last 30 years alone, technology transfer facilitated by the Bayh-Dole Act between federal supported universities and non-profits and the private sector contributed as much as:

• $3.3 trillion to U.S. gross economic output,
• $1.7 trillion to the U.S. GDP, and
• 6 million job-years of U.S. employment.

Since 1980, the annual number of patents on inventions benefiting from government funding has increased more than 70-fold.

And in more recent years, from 2001-2025, technology transfer at academic institutions led to the launch of more than 19,000 startups and the introduction of more than 17,000 new products. It has also seen:

• $288 billion in GDP,
• $577 billion in gross economic output, and
• 08 million job-years of U.S. employment.

In fact, universities and nonprofit research institutions averaged about 19,387 income-generating licenses annually from 2021–2025, that is roughly twice the annual average in 2001–2005.

And furthermore, the report found that there have been:

• 5,972 running-royalty licenses annually from 2021–2025,
• $3.2 billion in average annual gross licensing income, and
• $1.9 billion in average annual running royalty income.

And while that doesn’t necessarily translate one-to-one to on-the-market products, it does reflect the pace at which private-public partnerships are moving and continuing to grow.

Put simply, the legislation did not just spur economic development in the short term, but has continued to generate significant innovation, progress, and economic activity year after year—continuing today.

And the benefits are both micro and macro to economic development.

A closer look—the regional benefits of Bayh Dole

This economic impact Bayh-Dole has positively affected every corner of the United States, generating economic activity in every state in the union. The economic development from 2021–2025 alone is notable.

For example, in the South (AL, AR, DE, DC, FL, GA, KY, LA, MD, MS, NC, OK, PR, SC, TN, TX, VA, WV) Bayh-Dole helped facilitate 5,482 startups, and the development of 4,772 products.

Comparatively, in the West (AK, AZ, CA, CO, HI, ID, MT, NV, NM, OR, UT, WA, WY) Bayh-Dole helped facilitate 4,931 startups, and the development of 3,667 products.

And in the Northeast (CT, ME, MA, NH, NJ, NY, PA, RI, VT) Bayh-Dole helped facilitate 4,823 startups, and the development of 2,331 products.

And finally, in the Midwest (IL, IN, IA, KS, MI, MN, MO, NE, ND, OH, SD, WI) Bayh-Dole helped facilitate 3,791 startups, and the development of 6,482 products.

States like Pennsylvania, Massachusetts, California, and Texas benefited particularly with Pennsylvania seeing $4.49B in gross licensing income and $2.30B in running royalties; Massachusetts seeing $1.98B and $924M; California seeing $1.48B and $578M; and Texas seeing $905M; $876M.

Following up the lead, New York saw $911M in gross licensing income and $517M in running royalties; Georgia saw $655M and $598M; Minnesota saw $733M and $389M; and North Carolina saw $641M and $418M.

And finally, from 2001–2025, Pennsylvania reported the facilitated creation of 1,100 startups, Massachusetts 1,762, California 2,488, and Texas 1,101.

The impact on the growth of the biotechnology industry was especially seen in the Northeast and West regions.

As the report notes, in the Northeast: “Notable innovations benefiting from federal funding emerging from the region’s research institutions include the HIV/AIDS therapy Zerit from Yale University, high-definition video and audio technologies from Columbia University, and mRNA and CAR T-cell technologies from the University of Pennsylvania.”

While in the West: “The University of Arizona has used federal funding to develop…. innovations benefiting from federal funding for the early detection and prevention of osteoporosis began in University of Washington labs.”

The 2026 Bayh-Dole Report supports BIO’s own research

The numbers uncovered in the 2026 Bayh-Dole report are supported by BIO’s own commissioned report from AUTM.

When it comes to biotech and life sciences, this report found that biotech and life sciences licensing is especially impactful within the Bayh-Dole landscape. Historically, about 80% of university licensing income and 90% or more of hospital/research-institute licensing income has historically come from life sciences, while 60%–70% of licenses were to small companies or startups.

Ultimately, the picture is clear. The public-private collaboration built by the Bayh-Dole Act has changed the fact of biotech and life sciences innovation and development across the U.S.—and the world. And the lives saved, and improved, are likely incalculable.

Read “The Economic Impact of the Bayh-Dole Act.”

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According to details provided in the paper, which is titled “Tuning intracellular immunity by Nodamura virus B2 protein enhances self-1 amplifying RNA activity,” found that adding this protein, which is known to suppress RNA interference, reduced the extent to which the cells restrict saRNA, allowing it to provide far more of the intended protein in both stem cells and regular cells. It addresses a major challenge with saRNA vaccines that hampered their application in gene therapies, cancer immunotherapies, and protein replacement therapies. 

Most people are familiar with mRNA-based vaccines because of the Covid-19 pandemic. Since then scientists have worked on developing saRNA which replicates within host cells. The goal is to use the technology to develop vaccines and therapies that provide longer-lasting protection at lower doses that are safe and affordable.

Specifically, during the self-replicating process, saRNA generates double-stranded RNA which triggers cells’ anti-virus defenses. This makes the saRNA less stable, less able to replicate, and less able to instruct cells to produce the protein that trains the immune system. To date, this has limited the effectiveness of saRNA vaccines. But this development could help scientists develop effective saRNA vaccines that work at lower doses and could be rolled out further and faster than has been possible. 

According to Pierre Maillard, PhD, senior lecturer in antiviral immunity at Queen Mary University of London, and one of the authors on the study, “our findings identify a strategy to overcome a fundamental barrier limiting self-amplifying vaccines” and “if this translates successfully in vivo, it could open new possibilities for vaccine design as well for gene therapies and cancer treatment.”

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Nektar’s shares finished Friday flat, dipping 4% from $59.38 to $57.06 despite a jury siding with the San Francisco biotech over Eli Lilly (NYSE: LLY) in a three-year-old legal dispute over the pharma giant’s terminating a collaboration agreement to co-develop Nektar’s lead pipeline candidate rezpegaldesleukin (rezpeg).

A jury in the Northern District of California awarded Nektar $90 million, plus additional interest to be determined by the court, after agreeing with Nektar that Lilly breached a covenant of good faith and fair dealing implied through the companies’ up-to-$400 million agreement to co-develop rezpeg, initially for autoimmune and other chronic inflammatory conditions.

“We are pleased with the jury’s verdict in Nektar’s favor finding that Lilly breached the implied covenant of good faith and fair dealing in the license agreement,” Nektar said in a statement to GEN and other news outlets.

At deadline, a Lilly spokesperson had not responded to a GEN query seeking comment on the Nektar jury verdict.

The legal victory was ultimately viewed as anything but by investors, since Nektar had sought a verdict of $1 billion against Lilly. True, pre-market investors sparked a mini-buying surge that was enough to send Nektar shares rising ~4.92% early on Friday, Edward Nash, a managing director and senior biotechnology analyst with Canaccord Genuity, reported in a research note.

But when the opening bell sounded, Nektar shares swung back down, slipping 4.6% from an opening price of an even $60 a share the first minute of trading down to $57.22 at 9:48 a.m. That is below expectation based on the 34.14 million outstanding Nektar shares as of Friday morning.

“A judgment of $90M represents $2.64 in cash per share and would imply a 4.4% move upward in the stock compared to [Thursday]’s closing price of $59.38,” Nash explained.

Silver lining

Nash did see a silver lining behind the proverbial cloud of Nektar’s failure to surge on the good legal news.

“While the company was seeking $1B in damages and the $90M falls short of this number, our model does not include any windfall from the case. Importantly, the company also did not require any monies from the case in order to continue developing their pipeline assets,” Nash commented. “Therefore, any sum awarded in the case represents a non-dilutive capital addition to the balance sheet which we have not been factoring into our valuation.”

Because the jury’s verdict is still subject to post-trial proceedings and an all-but-expected appeals process, Canaccord Genuity has left out a jury verdict payout from its model for Nektar: “If Lilly appeals the verdict, it could be months or years before Nektar would receive any payment. We will move to include the sum in our model when and if it is paid.”

Nektar said rezpeg is a first-in-class therapeutic designed to target the CD25 sub-receptor in the interleukin-2 (IL-2) receptor complex to stimulate proliferation and growth of regulatory T cells (Tregs). By activating these cells, Nektar reasons, rezpeg could restore balance between Tregs and effector T cells (Teffs) and thus address the underlying immune system imbalance seen in many autoimmune and inflammatory conditions.

Dose-dependent AD improvement

In August, Nektar researchers published data in The Lancet from the 16-week induction period of the 52-week REZOLVE-AD trial (NCT06136741) assessing rezpeg in patients with moderate-to-severe atopic dermatitis (AD). Patients treated with rezpeg showed statistically significant, dose-dependent improvement in mean percent reduction in Eczema Area and Severity Index (EASI) from baseline at Week 16: 61% of patients dosed at the 24 μg/kg once every 2 weeks (q2w) arm; 58% of patients at the 18 μg/kg q2w arm, and 53% of patients dosed at 24 μg/kg once every 4 weeks (p<0.0001, p<0.0001, and p=0.0002, respectively), vs. 31% for placebo.

Nektar shares nearly doubled in February after it announced positive data from the 36-week blinded maintenance period of REZOLVE-AD. Among 55 patients dosed at 24 µg/kg every month, 71% (36) achieved EASI score reductions of at least 75% (EASI-75). Half those patients (18, or 80%) achieved EASI-90. The percentage climbed to 83% among the 56 patients receiving the same dosage of rezpeg every three months. Of those, 63% (21) maintained validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) 0/1 response after quarterly dosing, as did 85% (14) of patients dosed monthly.

Perhaps most encouraging to patients, 75% (25) of patients dosed monthly stopped itching—a percentage that rose to 77% (17) among those who were dosed every quarter.

AA durability data

In its Friday statement, Nektar said it recently advanced rezpeg into pivotal studies in AD and is initiating a pivotal study in alopecia areata (AA), where the company reported positive data in April from a blinded 16-week treatment extension period in its Phase IIb REZOLVE-AA trial (NCT06340360).

From week 36 to week 52, 29% of 14 patients at low dose of 18 µg/kg and 31% of 13 patients at high dose of 24 µg/kg achieved new SALT Score ≤20 responses as compared to none in the placebo arm. A SALT Score ≤20 is achieved when a patient has 80% or more of their scalp covered by hair.

“For me, as a scientist, this is really exciting, because most drugs are inhibitors,” Jonathan Zalevsky, PhD, Nektar’s chief research and development officer, told GEN in June in an interview during the 2026 Biotechnology Innovation Organization (BIO) International Convention, held in San Diego. “Inhibitors work at the beginning, and then they get worse, because it’s just how biology works. We always have escape pathways to any single inhibition. Repression requires workaround; that’s just basic biology. But rezpeg doesn’t work that way. It’s not an inhibitor. It’s healing your immune system, and it’s allowing you to resolve inflammation naturally, the way you’re normally meant to.”

“We think that might be one of the things we’re seeing reflected in the durability of rezpeg. It really seems much more durable than other mechanisms, and it has an activity that really preserves itself, and it long outlasts its own pharmacokinetics. That’s something we’re very excited about,” Zalevsky added.

The company has said it aims to submit a Biologics License Application (BLA) for rezpeg in AD in 2029.

“We remain focused on delivering this important potential new treatment as quickly as possible to patients battling chronic auto-immune conditions,” Nektar stated.

Relationship sours

Nektar’s relationship with Lilly soured in February 2023, soon after rezpeg failed the Phase II ISLAND trial (NCT04433585) in its initial development indication of moderately-to-severely active systemic lupus erythematosus (SLE). Lilly halted its collaboration immediately in that indication, followed by the companies determining whether to move forward in AD.

Two months later, Lilly handed back to Nektar all rights to rezpeg (which Lilly labeled LY3471851) in all indications, including AD and psoriasis. That ended a collaboration launched in 2017, when Lilly agreed to pay Nektar $150 million upfront and up to $250 million tied to achieving development and regulatory milestones toward rezpeg, then called NKTR-358.

Nektar responded to the termination in August 2023 by suing Lilly in U.S. District Court for the Northern District of California in San Francisco, alleging breach of contract and breach of implied covenant of good faith and fair dealing: “This case involves the all-too-familiar story of a large pharmaceutical company elevating profits over all else,” Nektar stated in its initial complaint.

In that complaint, Nektar asserted that Lilly failed to recruit enough patients for the ISLAND trial in lupus, leading to its failure. Nektar also alleged that Lilly incorrectly calculated data from the companies’ AD and psoriasis trials of rezpeg that was presented at the 2022 European Academy of Dermatology and Venereology (EADV) Congress; Lilly has denied the allegations on recruitment failures yet confirmed that the data were incorrectly calculated for both AD and psoriasis trials.

Clash over Dermira acquisition

Nektar also alleged—and Lilly has strongly denied—that the pharma giant soured, then sought to undermine, their collaboration after Lilly agreed to acquire Dermira for approximately $1.1 billion in 2020. Dermira focused on developing a pipeline of dermatological drugs led by lebrikizumab, a monoclonal antibody designed to bind IL-13 with high affinity. Today Lilly markets that drug under the name Ebglyss® (lebrikizumab-lbkz), following FDA approval in 2024 in moderate-to-severe AD.

Lilly then tried to get Nektar’s lawsuit dismissed—but when it couldn’t do so, it counter-sued, alleging breach of specified confidentiality provisions and defamation–a countersuit the pharma giant was allowed to voluntarily dismiss in October 2025.

A jury trial was initially scheduled to begin on October 27, 2025, was postponed due to the federal government shutdown, and instead began September 8, 2026. The case, Nektar Therapeutics v. Eli Lilly & Co (3:23-cv-03943), was assigned to Judge James Donato, who was appointed by President Barack Obama and confirmed by the U.S. Senate in 2014.

“In May 2023, after rezpeg failed to meet its primary endpoints in two separate Phase II trials, Lilly terminated its collaboration with Nektar and returned the rights to rezpeg at Nektar’s request,” Lilly told GEN in February 2026 through a spokesperson. “Our decision was consistent with Lilly’s normal practices and was made following a review of the compound’s competitive profile, including a high incidence of injection site reactions, which were also reflected in Nektar’s REZOLVE-AD trial.”

“The litigation between Lilly and Nektar remains ongoing, and we stand behind our decision to terminate the collaboration,” Lilly added at the time.

Anthropic’s “reminiscent of CRISPR” discovery dents gene editing stocks

Anthropic, the artificial intelligence (AI) giant that has filed for an initial public offering (IPO) that would value the company at an eye-popping $2 trillion, wreaked some havoc on gene editing stocks this past week after making global headlines with its announcement that its Claude large-language model “discovered a novel enzyme system with properties reminiscent of CRISPR, with only high-level direction from our scientists.”

The discovery emerged from a research group formed earlier this year “to see whether general AI models can systematize and accelerate discoveries capable of revolutionizing biology and medicine,” as Anthropic explained in its announcement. “Our focus is on fundamental biology research using Claude: exploring datasets of DNA to identify uncharacterized protein families, generating hypotheses at scale, and testing them through experiments in the lab.”

In one of the group’s first research programs, Claude autonomously discovered a novel enzyme system that is associated with an array of DNA repeats—what the company called “a pattern reminiscent of CRISPR.”

“Although we don’t yet know its function, the system that Claude discovered has a set of characteristics that have only ever been found together in a handful of other systems, all of which are programmable and perform operations like cutting, copying, and pasting DNA,” Anthropic explained.

Anthropic CEO Dario Amodei elaborated further in a post on X, describing the novel enzyme system as “a molecular machine that we suspect could represent a new gene editing mechanism. Its precise function, biotechnological utility (if any), or level of significance is not yet clear, but at minimum it is work I would have been proud to do as a PhD student.”

“Mostly” by Claude

“The work was done mostly, though not entirely, by Claude: our life sciences team suggested a broad area of research, Claude read through the literature and a bunch of genome data and discovered something interesting, then Claude proposed experiments to verify the discovery and our team carried them out,” Amodei added.

Anthropic’s statement and Amodei’s elaboration led investors to briefly sell off shares of gene editing company stocks on Wednesday, resulting in declines in high single digit percentages that day. The declines slowed down or turned into single digit gains Thursday, but the stocks all slid again Friday, albeit by low single digits.

Here’s how seven gene editing stocks performed between Tuesday and Friday:

• Beam Therapeutics (Nasdaq: BEAM)—Slipping 6% from $25.93 Tuesday to $24.37, finishing the week at $24.27.
• CRISPR Therapeutics (Nasdaq: CRSP)—Sliding 8% from $59.03 to $55.76, finishing at $54.23.
• Editas Medicine (Nasdaq: EDIT)—Shrinking 12% from $2.92 to $2.69, finishing at $2.58.
• Intellia Therapeutics (Nasdaq: NTLA)—Dropping 7% from $12.69 to $12.33, finishing at $11.75.
• Lenz Therapeutics (Nasdaq: LENZ)—Dipping 5% from $4.13 to $3.76, finishing at $3.92.
• Prime Medicine (Nasdaq: PRME)—Tumbling 18% from $3.54 to $3.13, finishing at $2.90.
• Q32 Bio (Nasdaq: QTTB)—Falling 17% from $10.57 to $9.56, finishing at $8.77.

Puneet Souda, senior managing director, life science tools and diagnostics and a senior research analyst with Leerink Partners, wrote in a research note that Anthropic’s discoveries along with other biotech-focused AI research would prove beneficial to life sciences tools companies—especially Twist Biosciences (Nasdaq: TWST), citing an earlier July 16 research note reporting that Twist has said its growth ramp of orders for its tools has grown by triple digits.

“We see TWST as the single most important beneficiary today from growing Bio AI efforts but expect all LST [life sciences tools] names to benefit in the long run as the need for automation and large-scale data grows (driven largely by industry funding vs academic),” Souda observed.

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Bacteriophages, or phages, are viruses that infect bacteria. Their ability to destroy bacterial cells has made them promising candidates for addressing antimicrobial resistance and reducing reliance on agrochemicals. However, many phage genes encode unknown functions, making it difficult to predict how the viruses behave or to modify them reliably.

“Our knowledge of phages is probably like the understanding of antibiotics back in the 1950s,” senior author Peter Fineran, PhD, said. “Many phage genes are currently in the area of microbial dark matter—encoding functions we just don’t understand—which is limiting our ability to use phages in healthcare and biotechnology.”

To address that gap, the team combined transposon insertion sequencing with CRISPR–anti-CRISPR selection. A transposon jumps into a phage genome and disrupts a gene. The selection system then recovers phages carrying those mutations, allowing researchers to determine which genes can be disrupted without preventing the virus from surviving and which are essential for phage function.

After establishing the mutagenesis workflow, the researchers extended it to introduce new genetic cargo. Rather than using the transposon only to disrupt genes, they loaded it with an additional sequence and inserted a fluorescent marker into phage genomes. The approach could also be used to add genes that help phages overcome bacterial defense systems, potentially improving their effectiveness against target pathogens.

“Once we had that established, we thought we could expand the technique and also use it to add genes directly into the phage genomes,” co-lead author Manuela Fuchs, PhD, said.

“This is a systematic, broadly applicable, and cost-effective way to not only investigate gene function, but also rapidly engineer phage genomes,” senior author Leah Smith, PhD, said, in a statement.

The platform could therefore serve two related goals: mapping the largely uncharacterized genetic landscape of phages and building variants with new capabilities. The researchers said the work opens opportunities for fundamental studies as well as future therapeutic development, although engineered phages would still require further testing to establish their safety and effectiveness in specific applications.

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The study, published in PLOS Pathogens, is entitled, “Targeted lysosomal activation in bladder epithelium enhances clearance of intracellular uropathogenic Escherichia coli.”

The findings suggest that the drug OM-89 (marketed as Uro-Vaxom^®) activates cellular degradation pathways in bladder epithelial cells while also increasing antibiotic uptake. OM-89 has been used for decades to help prevent recurrent UTIs. It is mainly known for stimulating the immune system, but the new study reveals a second mechanism of action: a direct effect on the cells lining the bladder.

The researchers studied mouse and human bladder epithelial cells using organoid models and differentiated cell cultures. They exposed the cells to OM-89, infected them with different strains of E. coli, and treated them with antibiotics. They then tracked bacterial survival, antibiotic uptake, and changes in cellular pathways involved in destroying intracellular material.

The findings show that OM-89 increased lysosomal acidification as well as the activity of lysosomal enzymes. When the researchers blocked lysosomal acidification, OM-89’s protective effect was lost, suggesting that lysosomal activity is directly involved in reducing bacterial regrowth in recurrent UTIs. In addition, OM-89 increased the accumulation of antibiotics inside bladder epithelial cells—an effect that extended across different antibiotic classes and several bacterial strains, including clinical samples from patients.

“We found that OM-89 doesn’t just stimulate the innate immune system as previously assumed,” says Kathrin Tomasek, PhD, project leader at the Laboratory of Microbiology and Microtechnology at EPFL. “It acts directly on bladder cells, strengthening their degradation pathways so they can destroy hidden bacteria more effectively while also helping antibiotics reach those bacteria—together reducing regrowth of the bacteria after treatment ends.”

The findings point toward a host-directed approach to recurrent infection: rather than targeting bacteria alone, treatment could also reinforce the antimicrobial machinery of the infected tissue itself.

More broadly, the study identifies lysosomal pathways in the bladder epithelium as a potential target for future treatment combinations designed to improve antibiotic outcomes.

“While the results come from preclinical models and do not change the approved indication or use of Uro-Vaxom^®, they deepen our understanding of how OM-89 may help strengthen the bladder’s natural defenses against recurrent infection and reinforce the scientific foundation supporting its use,” adds Christian Pasquali, senior scientific liaison director at OM Pharma and former head of preclinical research.

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Working with mouse and human models, the team discovered that stroke induces tumor microenvironment (TME) remodeling, alongside the emergence of a distinct population of tumor-associated astrocytes (TAAs) exhibiting reduced Ca²⁺ activity, and enrichment of tumor-associated microglia and macrophages (TAMs). Restoring TAA Ca²⁺  signaling or depleting TAMs, suppressed stroke-induced glioma progression, pointing to the importance of both cell type types in injury response.

Research lead Hyun Kyoung Lee, PhD, principal investigator at the Duncan NRI, and an associate professor of pediatrics – neurology and member of the Dan L Duncan Comprehensive Cancer Center at Baylor, and colleagues reported on their findings in Nature Cancer, in a paper titled “Stroke drives glioma progression through the emergence of tumor-associated astrocytes with reduced Ca²⁺ activity.” In their paper the investigators concluded, “Collectively, our findings establish stroke-induced remodeling of astrocytic Ca²⁺ signaling and TAMs as drivers of glioma progression and link brain injury to malignant disease.”

Glioblastoma (GBM) is the most prevalent and aggressive malignant brain tumor in adults,  and has what the researchers describe as “… a notably dismal 5-year survival rate.”  Research has catalogued a number of genetic mutations associated with GBM, the team pointed out, but the risk factors predisposing individuals to glioma are not well understood. “Recent clinical cohort studies and case reports have identified a correlation between glioma and brain injuries, where ischemic stroke shows significant co-occurrence with brain tumors, including glioma,” they further noted.

Lee added, “Epidemiological and clinical studies suggest that patients with a history of stroke or traumatic brain injury are at increased risk of developing brain tumors.  The risk can be about three-fold to seven-fold, depending on the age and sex of the patient.” However, Lee continued, “Despite these clinical observations, the mechanism that connects brain injury and cancer remains unclear.”

For their newly reported study the researchers, including Qi Ye, PhD, and graduate student Christine Madamba, at the Lee lab, worked with human and mouse models to investigate whether stroke promotes glioma growth and the factors mediating the connection. The team discovered the emergence of a distinct population of brain cells—tumor-associated astrocytes—with distinct physiological and molecular characteristics, including diminished calcium activity. TAAs were accompanied by the accumulation of two other cell types, remodeled tumor-associated microglia and immune cells called macrophages (TAMs). “Mechanistically, we identified SLC4A4 as a key regulator of Ca²⁺  activity in TAAs and CCL2-mediated TAM recruitment,” they reported in their study.

The researchers also showed that restoring TAA calcium signaling or removing TAMs suppressed stroke-induced glioma progression, “… identifying both populations as critical mediators of the stroke response.” The findings suggest that these injury-induced, tumor-promoting pathways are potential therapeutic targets and support continuing research into strategies that could reduce the risk of glioma growth in patients with a history of brain injury.

“We show that stroke promoted tumor infiltration into injured brain regions in human and mouse glioma models, and reduced overall survival,” Lee said. “Looking closer into the cellular and molecular makeup of the tumors, we found that stroke triggers remodeling of the tumor microenvironment.”

The authors stated “In summary, our study reveals that ischemic stroke remodels the TME to promote glioma progression, highlighting injury-induced tumor-promoting pathways as potential therapeutic targets for persons with a history of brain injury … More broadly, our work establishes a framework for investigating TAA-mediated immune regulation, TME remodeling, and the mechanisms linking brain injury to glioma progression and tumorigenesis.”

Lee added, “Our study supports that brain injury can be a risk factor for brain cancer. In addition, our findings contribute to growing evidence pointing at a role of astrocytes in brain tumor growth. Neuron-tumor interactions have been shown to contribute to cancer growth. We show that other brain cells, astrocytes, also seem to communicate with brain cancer cells and influence their behavior. They should be considered when studying cancer mechanisms and therapies.”

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“SFC is a platform technology that utilizes upcycled CO₂ for purification of natural  and synthetic molecules that is both highly efficient and sustainable at the same time,” said Palcic. “ExtrateX’s deep expertise in supercritical CO₂ systems and strong presence across Europe make them the ideal partner.”

According to Gonzague Choppe, CEO of ExtrateX, “This strategic collaboration brings together the complementary strengths of two companies with extensive expertise in supercritical fluid technologies. Thar Process brings some of the most advanced SFC solutions and deep chromatography expertise, while ExtrateX contributes its extensive experience in supercritical fluid technologies, process expertise, scale-up capabilities and strong European presence.”

The partnership becomes effective on the first day of 2027, with ExtrateX establishing sales and support operations to serve European customers. The company will handle equipment sales, technical installation, maintenance, and customer training.

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Around this time last year I was attending an aging conference in Manchester, listening to a talk about fly aging, when my phone started pinging. News outlets were reporting that a hot mic had caught Russia’s and China’s leaders discussing the possibility of living forever.

“With the developments of biotechnology, human organs can be continuously transplanted, and people can live younger and younger, and even achieve immortality,” Russia’s Vladimir Putin reportedly told China’s Xi Jinping.

He seems to have been referring to the “replacement” theory of longevity, which has been supported by multiple experiments that involved physically stitching young mice to old ones. Something about the young blood rejuvenated the old mice. Perhaps young organs could rejuvenate world leaders in their 70s, too.

Unfortunately for Putin, new research pours a little cold water on this idea. Studies on transplanted hearts in both mice and humans suggest that new hearts soon adopt the biological age of the recipient, no matter how young they were to begin with. The finding could be important for transplantation, but it also highlights just how complex aging—and rejuvenation—are.

Jesse Poganik at Brigham and Women’s Hospital in Boston is one of the many scientists trying to understand exactly what it is about the bodies of young mice that rejuvenates old ones. Plenty of research has focused on seeking the secrets of youth in young blood. But what if it’s something about young organs instead?

To find out, he and his colleagues performed a set of heart transplants in mice. In humans, heart transplants typically involve removing a damaged or injured heart and replacing it with another from a donor who is usually much younger than the recipient. (When Poganik assessed hospital records, he found that most recipients were about 20 years older than their donors.)

The mouse transplants were different: Mice received a second heart, implanted in the neck—a procedure that’s slightly simpler and allows scientists to compare the new hearts with the existing ones. In some cases, young adult mice were given a heart from a middle-aged donor. In others, middle-aged mice got young hearts.

The team used a trio of “aging clocks”—molecular tools used to estimate the biological ages of tissues and whole organisms—to assess whether the additional hearts affected the mice in any way. These clocks were good at predicting the chronological age of mice that didn’t get new hearts.

Poganik says he was expecting to see a reciprocal effect, and that young hearts might benefit older animals, for example. In previous work by other members of his team, young mice that got old hearts experienced a buildup of senescent cells in their other organs. These cells are thought to contribute to the aging process, suggesting that receiving an old organ might prematurely age an animal.

But that’s not what he found. When he and his colleagues analyzed the transplanted hearts between four and six months after surgery, they found that the hearts seemed to have adopted the biological age of the recipients. Young hearts got older, and old hearts got younger. “The environment of the transplanted organ really dictates how it seems to behave biologically,” he says. The findings were published online at bioRxiv last week.

The team also looked at each mouse’s blood and other organs—including its original heart—and were surprised to find that they seemed to be unaffected by the presence of the new heart, despite the age of its donor.

The finding was backed up by data from human heart transplants. People who receive a donor heart must typically undergo a series of heart biopsies after surgery. The tiny pieces of heart tissue collected from people who had heart transplants at Brigham and Women’s have been stored for decades. And when Poganik and his colleagues tested their biological ages with the aging clocks, they found a similar pattern: No matter the age of the donor, a new heart quickly adopts the biological age of the person who received it.

It’s not clear why this is, but João Pedro de Magalhães, who studies aging at the University of Birmingham in the UK and was not involved in the study, thinks it might have something to do with the recipient’s immune system. Perhaps immune cells circulating in the blood might affect markers of aging in the new organ, he says.

Perhaps the potential rejuvenating effects of a young heart end up being diluted by all the other aged components of an older body, Poganik suggests. Or maybe a single organ just isn’t enough to see an effect.

Poganik hopes his finding will encourage surgeons to consider using hearts from older donors, many of which are discarded on the assumption they won’t function as well. (Machines used to preserve organs before transplantation are changing that already—and Poganik has worked on another study showing that these devices seem to rejuvenate donor livers to some extent.)

But the study also highlights just how complicated aging is. If organs seem to be getting older by one measure but not by another, how can we get a full picture of the biological age of an organ, or a person?

This complexity means that scientists are not likely to discover a true way to completely reverse aging, says Poganik. “That would mean that every aspect of aging has to go back in time,” he says. Reversing DNA damage, structural damage, and all the other degradations that are part of the aging package, across all our various cells and tissues, presents an enormous challenge.

“There are aspects of biological age that are probably reversible, and there are aspects that are probably not,” he says. Sorry, Putin.

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

So says Guy Rachmuth, from Seattle services firm Just – Evotec Biologics, who told GEN, “Cell culture media requires significant footprint for both batching and storing media, including cold temperature storage for many final liquid media formulations.

“Manufacturers often need tens to hundreds of thousands of liters of media, making storage efficiency an increasingly important consideration. In addition, mixing equipment limitations can necessitate compounding multiple media batches per run and increase operational complexity in manufacturing.”

Rachmuth added, “These challenges become even more pronounced in intensified production processes, where continuous perfusion of bioreactors significantly increases cell culture medium volume requirements.”

With this in mind, Just – Evotec developed J.Media, a concentrated, room-temperature stable powder format that, the firm claims, reduces storage footprint, simplifies logistics and supports more flexible and efficient manufacturing operations.

The product was developed to meet the demands of Just – Evotec’s own manufacturing programs and has since become a core platform technology across the organization supporting nearly 70 projects.

Rachmuth told us, “Given the success we’ve seen internally, we recognized an opportunity to make J.Media available more broadly to the industry. By offering it as a standalone product, we aim to help other organizations benefit from the same combination of productivity, scalability, and cost efficiency.”

In tests, details of which were presented at the BPI conference and exhibition in Boston, the media outperformed several commercially available products, exhibiting higher volumetric productivity and cumulative titer.

According to Rachmuth, “The media routinely runs at 80-100 10E6 cells/mL maintaining high viability over a period of 15-25 days, or longer. Our productivity is higher than competitor media.

“In perfusion operations, volumetric productivities of up to 4-5 g/L/day have been achieved, highlighting the platform’s ability to support highly efficient manufacturing processes,” he said.

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Cellufine is JNC’s family of cellulose-based chromatography media for biopharmaceutical purification. The company’s newer MLP platform takes that foundation in a different direction by using a large-pore bead architecture intended to improve access for bulky biological targets that can be difficult to accommodate with conventional porous media.

That design was the focus of a presentation by Chigusa Mori, R&D scientist at JNC, titled “Cellufine MLP: Wide Pore Cellulose Base Bead 3D Architecture for Large Biomolecule Chromatography Applications.”

JNC is also highlighting two development-stage MLP products through poster presentations. One examines Cellufine MLP DexQ for separating empty and full adeno-associated virus (AAV) particles, which is a persistent purification challenge in AAV manufacturing. Another explores Cellufine MLP DexS for viral-vector purification.

MLP DexS uses dextran sulfate as a ligand and is being investigated for large-particle applications, including vaccines. Data reported by JNC show that the resin concentrated inactivated influenza virus 13-fold while cutting protein impurities by 90.3%. In testing with human coronavirus OC43, JNC reported a 97.3% reduction in protein impurities together with 91% virus recovery. Those results point to the broader bioprocessing question behind JNC’s showcase: how chromatography can evolve as therapeutic modalities move beyond traditional proteins toward particles and assemblies with very different physical properties.

For downstream developers, pore architecture is becoming more than a resin-design detail. It can determine how effectively large targets enter the bead, interact with ligands, and ultimately separate from process-related impurities.

By bringing its MLP technology to BPI26, JNC is positioning large-pore cellulose chromatography as one approach to extending conventional column purification into areas where the size of the product itself increasingly shapes process performance.

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Kudryashev is senior and corresponding author of the scientists’ published paper in Nature Communications, titled “Ligand-induced activation of RyR1 in native membranes,” in which they conclude that their findings “… explain the mechanism of ligand-gated activation of RyR1 in native membranes and provide structural insights critical for understanding RyR1-associated skeletal muscle diseases and developing targeted therapeutic strategies.”

Skeletal muscle contraction relies on “… a precise interplay between electrical signals and Ca2+ release from internal stores,” the authors explained. Maintaining readiness for contraction, the cells keep calcium locked in this internal compartment, the sarcoplasmic reticulum (SR). Studding its membrane are thousands of RyR1 channels—the largest known ion channels—containing pores that release calcium.

For a muscle to contract properly, RyR1 channels must open synchronously via a mechanism known as “coupled gating.” How they accomplish this has been unclear since it was described almost 30 years ago. “…  the physical mechanism orchestrating this cooperativity has remained unknown,” the authors noted in their paper.

Through their reported studies Mikirtumov, Kudryashev, and colleagues have captured the first high-resolution 3D images of RyR1 at six stages of opening inside the intact sarcoplasmic reticulum membrane. The structure of RyR1 has been described before, but previous studies used channels that had been removed from the membrane. Instead, the Kudryashev lab studied the structure of RyR1 in its natural environment using the advanced imaging techniques of cryo-EM and tomography. “Because RyR1 is a membrane protein, you have to pull it out with detergents to purify it. But that environment can be disruptive to such a sensitive protein,” explained Mikirtumov, who is now a postdoctoral researcher in the lab of Christian Spahn at Charité – Universitätsmedizin Berlin. “We wanted to capture the structure of the channel in its native membrane and find out whether its opening mechanism looks different there.”

The team isolated the SR from rabbit muscle and imaged it at the Core Facility for Cryo-Electron Microscopy, which is run jointly by Charité – Universitätsmedizin Berlin, the Max Delbrück Center, and the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP). The Kudryashev lab has specialized expertise in cryo-EM and tomography and the computational tools necessary to analyze the resulting data.

“We shoot electrons through the sample and take thousands of pictures, each with many copies of the same protein,” explained Mikirtumov. “Then we average them all together, and that gives us a high-resolution 3D reconstruction.”

By adding small molecules to initiate channel opening, the researchers caught RyR1 at six stages between fully closed and fully open. “Comparing the structures revealed the full opening motion: The bulky outer part rotates within the plane of the membrane, like turning the ring of a camera lens, while the pore in the channel widens to roughly twice its original width.

The resulting images showed that neighboring channels remain in contact with each other when transitioning from the closed to open states. This contact, or interface, mediates coupled gating: as one channel rotates open, it strains the interface with its neighbor, making it easier for that channel to rotate and open too. “It’s like the cogs in a clock,” said Kudryashev. “Once one cog turns, it primes its neighbors to turn, too.”

In their paper the team wrote in summary, “The RyR1 structures in four distinct as well as two intermediate functional states induced by activating ligands showed that the activation of RyR1 includes a large rotation component in the membrane plane. The structures reveal direct, corner-to-corner physical contacts between receptors, providing a high-resolution view of the interface that mediates coupled gating.”

Using cryo-electron tomography, the team also imaged pairs of neighboring channels at five stages of opening. They found neighboring channels were more likely to be synchronized, and that two interacting closed channels were more stable than two closed channels in isolation. These findings support coupled gating and suggest that channels hold each other shut.

Mutations in the RYR1 gene cause malignant hyperthermia, a life-threatening reaction to some anesthetics, and congenital myopathies that weaken muscles. Many of these mutations alter the channel exactly where it touches its neighbor.

Mikirtumov added, “A lot of these mutations don’t seem to affect how a single channel opens, but rather how channels cooperate with their neighbors. We mapped several of them onto the interface, and we think that in these cases, it’s the cooperation between channels that breaks down.”

The researchers propose that disruption at the interface between channels makes them leaky, releasing calcium when they should retain it. This makes the interface itself a target for therapies. “We propose a mechanism for RyR1 activation, shifting the focus from an individual channel event to a cooperative process orchestrated by a mechanically coupled receptor lattice,” they stated.

The team is already testing the idea. “We need to prevent the channels from opening spontaneously,” said Kudryashev. “Now that we know how the inactive state is organized, we can design biologics or small molecules to stabilize this closed state.” The authors concluded, “These results emphasize the physiological importance of RyR1 arrays as integrated functional units and provide new perspectives on EC-coupling and the development of targeted therapeutics for RyR1-linked channelopathies.”

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Both studies are led by scientists at the Icahn School of Medicine at Mount Sinai. They help answer questions about the exact mechanism by which blood vessels deteriorate as Alzheimer’s progresses, particularly in people with APOE4. The Cell study details how the Mount Sinai researchers combined existing datasets to create a single-cell transcriptomic atlas of the human brain’s vasculature, resulting in a detailed map of gene activity across cells that form and support blood vessels. 

By analyzing the map, they found that APOE4 caused pericytes, which are cells that stabilize small blood vessels and help maintain the blood-brain barrier, to transform into scar-forming myofibroblast-like cells. This change promoted vascular fibrosis and increased amyloid accumulation around the vessels. This created conditions that may compromise blood flow and promote neurodegeneration. Using aged APOE4 mice, the scientists observed the effects of blocking TGF-β signaling, a pathway involved in cellular communication and tissue remodeling. They found that it restored pericyte coverage and reduced both fibrosis and vascular amyloid, effectively demonstrating that it may be possible to reverse APOE4-associated cerebrovascular degeneration therapeutically.

These results show that “damage to the brain’s blood vessels is not simply a late consequence of Alzheimer’s disease; it is a biologically active process caused by APOE4 that may be reversible,” said Joel Blanchard, PhD, associate professor of neuroscience, and stem cell biology and regenerative medicine at Mount Sinai and a corresponding author on the study. Furthermore, “ through our experiments, we were able to block this protein buildup process, revealing possible new therapeutic treatment options and strategies for protecting the brain’s circulation in people at high genetic risk for Alzheimer’s disease,” said Braxton Schuldt, MD/PhD candidate in neuroscience and researcher in the Blanchard Laboratory at Mount Sinai. He is also the first author on the paper. 

For the Cell Stem Cell study, the Mount Sinai scientists and their collaborators elsewhere used miBrains to investigate how APOE4 promotes abnormal protein build up in diseases like Alzheimer’s and Parkinson’s. Derived from induced pluripotent stem cells, miBrains are three-dimensional human brain tissues developed by the Mount Sinai team to model key features of the human brain and its vascular network. These 3D tissues contain all the major cell types, including neurons, supporting glial cells, myelin-producing cells, and cells that form blood vessels. 

They also mimic the behavior of human brains carrying APOE4. Specifically, miBrains carrying APOE4 accumulate higher levels of abnormal alpha-synuclein, the protein commonly associated with Lewy body dementia and Parkinson’s disease. Experiments reported in the paper showed that APOE4 causes cholesterol to accumulate in astrocytes, and that this excess cholesterol impairs the astrocytes’ lysosomal waste-disposal system, reducing their ability to break down alpha-synuclein. The protein instead aggregates and spreads to neurons, leading to harmful protein deposits. The findings identify cholesterol metabolism in astrocytes and lysosomal function as promising therapeutic targets for Alzheimer’s and Parkinson’s disease.

“A key advance of our technology is that miBrains with predefined cellular compositions and disease-related factors can be cryopreserved,” said Louise Mesentier-Louro, PhD, assistant professor of neuroscience, and stem cell biology and regenerative medicine at Mount Sinai and first author of the study. “This capability improves reproducibility and scalability of complex disease modeling and supports more efficient drug development and validation.”

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These changes include a new Strategic Breakthrough Program, which can bring up to $30 million to impactful innovations addressing pediatric and rare cancers, experts from the National Cancer Institute (NCI) told a Sept. 17 webinar for the Council of State Bioscience Associations (CSBA).

Their presentations offer useful information for oncology biotechs, and any biotech needing seed funding to start their work.

“We tend to be the first source of funds that a company will look for after they’ve raised funds from friends and family,” said Michael Weingarten, Director of NCI’s SBIR Program.

Organized by the Biotechnology Innovation Organization (BIO) as a service for its state affiliates in the CSBA, the webinar covered National Institutes of Health (NIH) Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants—particularly NCI cancer research grants.

About SBIR/STTR

The most recent changes to SBIR and STTR were added in March, when the programs were reauthorized by Congress until September 2031. The next application deadline is Jan. 5, which is why this information matters now, the experts told the webinar.

Much of the conversation focused on SBIR grants, which individual start-ups can seek by themselves. STTR grants tend to be larger and support technology transfer. Along with a start-up, STTR grants must include an institutional partner, such as a university, that is transferring the technology.

The impact for start-ups, and American innovation, can be huge. Weingarten cited a 2018 study of Phase II SBIR/STTR grants given out by the NCI for cancer work between 1998-2010. Of those 690 projects, 247 went commercial, achieving over $26 billion in total economic output nationwide and creating over 108,000 jobs with an average salary of $75,000.

“We invested a total of $787 million in those companies to produce that $26 billion return. So overall return on investment for NCI’s money was about 33-to-1,” he said.

The new Breakthrough Program

One of the changes in the SBIR program that received special focus during the webinar was the new Strategic Breakthrough Award. The program can bring a start-up developing an important innovation for an unmet need as much as $30 million in capital at a critical phase of development, explained Billy Baza, Program Director within the NCI SBI Development Center.

“It really has to be a significant improvement to existing standard of care,” said Baza, describing the type of innovation targeted by the Breakthrough Award. “It really has to have an impact on the patients.”

The Strategic Breakthrough Awards differ among the various institutes of the NIH. At the NCI, “our goal is to really fund pivotal clinical studies for pediatric and rare cancers,” Weingarten said.

Investigation showed that the largest amount of private venture capital for oncology development goes to the most common types of cancer. NCI is hoping this program will encourage private investment in the rarer cancers, Baza said.

One way the program attracts private capital is through its 1-to-1 matching provision: applicants must use the grant to attract an equal amount of external funding, whether from a private investor, a partner company or another government program.

“Matching funds need to be secured after the application is submitted, but before the award is made,” Baza said. “That means you’re going to have explain your matching capital fundraising strategy within the commercialization plan.”

Other requirements, according to Baza:

• “The technology has to be at a clinical stage, with some promising early human clinical data as well.”
• Patient unmet need has to be clearly demonstrated. “We’re not looking for incremental improvements,” Baza said. “We want innovations that can really impact high-need patient populations.”
• There must be a credible study plan addressing clinical trial operation and enrollment, and strong interactions with the Food and Drug Administration (FDA).

It can also help to show applicants are receiving FDA support, including Fast Track and orphan designation, or accelerated approval allowing use of surrogate endpoints.

Other procedural and funding changes

Weingarten outlined several changes under the newly reauthorized programs, including a limit of nine applications a year to Health and Human Services SBIR programs. One helpful change allows applicants seeking their first STTR grants to apply for “Direct to Phase II Award,” receiving higher Phase II funding right away without going through Phase I.

Weingarten also discussed the amounts of the awards available from NCI, including changes in those awards:

• The relatively new Concept Award provides very early-stage SBIR funding for a technology that is still just a concept, without supporting data. “We are looking for out-of-the-box ideas and disruptive technologies in the areas of pediatric or rare cancers,” Weingarten said. Applicants can receive up to $300,000.
• NCI increased Phase I awards from a maximum of $400,000 to $700,000. “Typically, those are for proof-of-concept studies,” Weingarten said.
• NCI Phase II awards go up to $2.5 million, usually for 2-3 years. “We tend to think of Phase II as funding IND enabling work,” he said.
• The Commercialization Readiness Program (CRP), for post Phase II, funds early clinical studies and provides up to $4.2 million.
• The above-mentioned Strategic Breakthrough Program is capped at $15 million from SBIR, before private matching funds are added.

“If you look across all these different funding streams, companies can access up to $22 million in funding from our program, which is larger than award sizes from any of the other institutes at the NIH,” Weingarten said.

To learn more:

• Join NCI’s training on how to apply for SBIR/STTR grants.
• NCI SBIR web site.

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The inspection supported the European Union marketing authorization application for a biologics product from a biopharmaceutical client. The EMA inspection involved an assessment covering the full biologics manufacturing lifecycle and a review of the facility’s quality systems and operational performance.

The Suzhou facility’s quality management system, infrastructure, technical capabilities, data integrity controls and organizational management were recognized by the EMA, according to the company. The company’s Quality Risk Management (QRM) framework has enabled proactive identification of compliance risks, reduced uncertainties associated with cross-regional technology transfer, and provided greater predictability as innovative therapies advance toward global regulatory submission and commercialization, stated Kaisong Zhou, PhD, chairman and CEO of Altruist Biologics.

“Quality spans the entire biologics lifecycle, ensuring compliance with rigorous regulatory requirements from development through commercialization,” he said. “The recent EMA GMP certification exemplifies that our robust manufacturing processes, quality systems, talent and world-class facility meet regulatory requirements, and we have the agency’s trust to manufacture and deliver products on behalf of our global partners and the patients they serve.”

Altruist’s Suzhou and Hangzhou sites are designed and operated to meet GMP requirements across multiple regulatory authorities, including the EMA, FDA, the Pharmaceutical and Medical Devices Agency (PMDA) of Japan, and the National Medical Products Administration (NMPA) of China, pointed out Zhou.

Equipped with 60,000 liters of antibody manufacturing capacity and an ADC clinical manufacturing line, the Suzhou facility provides end-to-end services for antibodies, fusion proteins and antibody-drug conjugates, he continued. The Hangzhou site is designed with a total antibody manufacturing capacity of 172,000 liters, with 80,000 liters currently operational across four 20,000-liter stainless steel bioreactors. A 2,000-liter antibody production line is currently under construction and is expected to be operational by mid-2027.

Altruist collectively has 140,000 liters of operational CDMO manufacturing capacity, representing approximately 20% of China’s total capacity, explained Zhou. As additional planned capacity comes online, Altruist’s total manufacturing capacity is expected to reach 232,000 liters.

In addition to the EMA, the Suzhou site has received multiple recognitions from other global regulatory authorities, said Zhou. It has successfully completed remote interactive evaluation by the FDA, and has passed inspections by the NMPA and the Federal Committee for Protection from Sanitary Risks (COFEPRIS) of Mexico, as well as more than 40 quality audits conducted by global clients.

Altruist Biologics, which will be exhibiting at booth 1027 at BPI, is a wholly-owned subsidiary of Innovent Biologics.

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Basecamp, a frontier AI company focused on therapeutic design, focuses on leveraging EDEN (short for “environmentally-derived evolutionary network), its biological foundation model, to develop in vivo cell therapies designed to reprogram a patient’s cells inside the body.

EDEN is Basecamp’s new class of foundation models trained on what the company says is the world’s largest and most diverse evolutionary dataset. According to Basecamp, EDEN offers the ability to design long and complex DNA sequences with large serine recombinases capable of delivering those sequences precisely.

EDEN-designed cell therapies are also designed to overcome the high manufacturing cost and limited complexity of present-day cell therapies. As a result, Basecamp said in its announcement, its EDEN-designed therapeutics offer the potential to treat complex diseases that include cancer and autoimmune disease, aiming “to underpin the future of cell therapies, making them more sophisticated, more customizable and simpler to administer” than current cell therapies.

“We believe the future of medicine lies in reprogramming the body to repair itself. We design the models and the medicines to teach it how,” Glen Gowers, PhD, Basecamp’s co-founder and CEO, said in the statement. Gowers co-founded Basecamp with Oliver Vince, PhD.

Basecamp says it has shown strong preclinical results across multiple modalities and disease areas. Aiming to expand its partnerships with biopharmas, Basecamp in April appointed Richard Pearce as chief business officer. Pearce previously served as Biogen’s head of business development, strategy, and portfolio management.

“AI-based approaches promise to change what’s possible for patients who currently have few alternatives. This funding brings this technology closer to those who need it most,” Gowers added.

Prominent investors

One prominent investor participating in the financing is Silicon Valley-based VC firm Menlo Ventures, which invested in Basecamp through the Menlo Anthology Fund, a $100 million fund financed by Menlo Ventures and launched in 2024 in partnership with Anthropic, the AI model builder behind the Claude family of large language models. Startups financed by the Menlo Anthology Fund receive access to Anthropic products and research, $25,000 in free credits towards Anthropic’s most advanced models, and what the company calls “best-in-class” venture support from Menlo.

“We’re particularly interested in ventures that leverage AI to enhance human capabilities and productivity in fields such as healthcare, legal services, education, energy, infrastructure, and scientific research,” Daniela Amodei, Anthropic’s co-founder and president, stated in announcing the launch of the Menlo Anthology Fund.

Anthropic’s offerings include Claude Science, the AI research workbench launched in June and featuring Basecamp’s antibiotic design and vaccine prediction AI models.

Another prominent investor is NVentures, the venture capital arm of Nvidia—the Silicon Valley microprocessing giant with which Basecamp has leveraged AI to unlock programmable gene insertion, which places large therapeutic DNA sequences at precise locations in the human genome.

Researchers from Nvidia joined partners from Basecamp, Microsoft, and two research institutions in detailing EDEN in a preprint posted January 12 on bioRxiv.

63% hit rate

The investigators showed EDEN to achieve an overall functional hit rate of 63.2% across diverse DNA prompts when prompted on only 30bp of DNA from outside the training data. Half (50%) of EDEN-generated LSRs were active in human cells, achieving therapeutically relevant levels of chimeric antigen receptor (CAR) insertion in primary human T cells. Also, an EDEN-generated synthetic microbiome was shown in the preprint to cover 9,067 species with a biome-specific taxonomic accuracy of 99%.

Nvidia and Anthropic were among partners of Basecamp that built its Trillion Gene Atlas, which draws on biological data collected through access and benefit-sharing partnerships in more than 30 countries across all seven continents. The Atlas is at the center of Basecamp’s AI platform, and according to the company is the world’s largest proprietary biological AI training dataset. Pacific Biosciences of California (PacBio) and Ultima Genomics also partnered in building the Atlas.

Trained on data from the Atlas, Basecamp’s EDEN models deliver a universal understanding of how DNA works across all of life. Its capabilities include designing cell and gene therapies, enzymes and peptides.

Unlike AI systems developed for a single scientific task, EDEN models are trained to recognize patterns across biology. As a result, it can generate potential therapeutic candidates directly from information about a disease, an approach already demonstrated through Basecamp’s collaboration with Anthropic on Claude Science.

Anthropic and NVentures are among participants in the financing, along with Catalio, European Tech Collective, Firebrand River Capital, King Philanthropies, NATO Innovation Fund, Redalpine, The Rockefeller Foundation, Singular, Sovereign AI, and True Ventures.

‘Next transformation’

Basecamp has garnered additional investment from senior leaders across biopharma and global industry, including André Hoffmann, vice chairman of Roche, a board member of Roche subsidiary Genentech, and co-chair of the World Economic Forum.

“The biotechnology revolution that began fifty years ago transformed how we make medicines. Personalized, AI-designed therapeutics represent the next transformation of that journey,” Hoffmann stated. “Basecamp Research has built the full platform to deliver it, from biological data to trained models to designed therapies. This will be key in helping the industry to continue to innovate.”

Basecamp raised $60 million in Series B financing in 2024, and a $20 million Series A round two years earlier.

The Series C financing was led by S32, a Palo Alto, CA-based venture firm. S32 has about $3.5 billion in assets under management after closing earlier this year on a $517 million sixth flagship fund, according to PitchBook.

As a result of the latest financing, Andy Conrad, General Partner at S32 and former CEO of Google’s Verily, will join Basecamp’s board.

“AI is opening up new possibilities across every part of society, but perhaps nowhere is the potential more meaningful than in human health. The ability to combine AI, biological data and scientific insight could transform how we understand disease, discover medicines and ultimately improve and extend people’s lives,” Conrad stated. “Basecamp Research is building an important technology platform at the center of that opportunity.”

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Initial results from this collaboration will be presented this week at the Pancreatic Cancer Action Network (PanCAN)’s 2026 Scientific Summit in San Diego.

Recent advances in targeted therapies for pancreatic cancer have brought renewed attention to PDAC and underscored the need for better strategies to identify which patients are most likely to benefit from new treatments. Inventia’s RASTRUM platform prints reproducible 3D pancreatic cancer models in which tumor and stromal components can be controlled and perturbed independently.

Genialis characterizes those models with the Genialis Supermodel—a large molecular model trained on a proprietary harmonized and curated transcriptomics dataset— and connects them to molecular states observed in the clinic. The collaboration also draws on data generated through Genialis’ long standing collaboration with PanCAN.

In the study being presented on Friday, September 25, Genialis identified PDAC patients with poor prognosis based on the composition and activity of the tumor microenvironment across 644 pancreatic cancer patient tumors taken from the PanCAN SPARK “Know Your Tumor” cohort.

“This collaboration closes an important gap in drug discovery by connecting what we learn from patients with what we can test in the lab,” said Cameron Ferris, PhD, CEO and co-founder of Inventia Life Science. “Genialis can identify clinically meaningful biological states in real tumors, while RASTRUM allows us to model and perturb those states at scale. Together, that creates a powerful way to generate and test therapeutic hypotheses that are grounded in the biology of the patients we ultimately want to treat.”

The design closes a loop that translational programs usually leave open: hypotheses are derived from patient data, tested experimentally in human-relevant systems, and returned to the clinical population to determine where they are most likely to apply, noted Ferris.

“Our pharma partners need to make critical decisions about which patients to enroll and which combinations to pursue, yet historically, whether a preclinical result would translate to patients often wasn’t clear until Phase II,” said Rafael Rosenbarten PhD, CEO and co-founder of Genialis. “Inventia gives us a model where we can test those hypotheses experimentally, while the Supermodel helps identify the patients most likely to benefit.”

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The team’s research, headed by Yingkai Zhang, PhD, professor of chemistry at NYU, addresses a longstanding challenge in molecular design and drug discovery, which is how to rapidly and reliably determine the stable form of molecules that share a molecular formula but readily convert into different forms. The researchers have released their method as an open-source tool, Tautomer-Predictor, which can rapidly analyze very large molecular libraries.  Zhang is senior author of the scientists’ published paper in Chemical Science (“Deep learning of tautomer stability from crystallographic proton positions.”)

Many drug-like molecules can exist in two or more closely related forms called tautomers. A hydrogen atom moves from one site to another, accompanied by a change in the bonding pattern. “Although this may seem like a small change, different tautomers of the same molecule can alter how a molecule interacts with a protein target,” explained Zhang. “Correct tautomer assignment is consequently important for molecular modeling and structure-based drug discovery.”

And as the team noted in their paper, “… incorrect tautomer assignment can compromise molecular docking, free-energy calculations, virtual screening, and other tasks in structure-based drug design.”

However, determining the correct tautomer remains a challenge—akin to finding a needle in a moving haystack. The scientists further commented, “Tautomerism plays a central role in molecular recognition, physicochemical properties, and chemical reactivity, yet rapid identification of stable tautomeric states remains a persistent challenge in molecular design and structure-based drug discovery.”

This challenge exists, in part, because of a scarcity of experimental data that characterizes tautomer structures. For instance, in the Protein Data Bank, a worldwide repository of the 3D structures of large biological molecules that is widely used in biological research, the location of hydrogen atoms that distinguish one tautomer from another are typically not available. The Protein Data Bank contains molecular structures that are largely determined using experimental methods such as X-ray crystallography, but the resolution of macromolecular X-ray structures is generally insufficient to locate the position of hydrogen atoms reliably. As a result, hydrogen positions—and therefore the tautomeric state of a molecule—often have to be inferred by scientists.

Other methods also fall short. Using quantum mechanics to assess tautomers is often too computationally demanding and expensive for screening full libraries, while machine learning is limited by the relatively small datasets of experimentally characterized tautomers in solution, which tend to contain only a few hundred molecules. “A variety of computational methods have been developed to address tautomer prediction, but each faces important trade-offs between accuracy, throughput, and generalizability,” Zhang et al. stated.

In contrast, many high-resolution small-molecule X-ray crystal structures in the Cambridge Structural Database (CSD)—the largest repository of experimental crystal structures in the world—show the position of hydrogen atoms. “Because many CSD structures contain explicitly assigned hydrogen atoms, they offer direct experimental information about tautomeric states in the crystalline environment,” the authors pointed out. “We realized that experimentally resolved hydrogen positions in high-resolution small-molecule crystal structures provide a largely untapped source of experimental information about tautomer stability,” added Zhang, who is also part of the NYU Simons Center for Computational Physical Chemistry.

When the researchers applied their model to 5,075 PDBbind ligands—biomolecular complexes found in the Protein Data Bank—with multiple possible tautomeric states, they identified 126 cases—approximately 2.5%—in which the assigned ligand tautomer was likely incorrect. In each of these cases, the model reassigned an alternative stable tautomer, which showed improved hydrogen bonding patterns.

“Reassigning these tautomers generally produced more chemically reasonable interactions,” noted Zhang. “This does not mean that the experimentally determined protein structures themselves are incorrect; rather, our results suggest that the previously assigned chemical representation may warrant revision.”

For instance, in one of the molecules in the Protein Data Bank, the AI model predicted a tautomer with a differently positioned hydrogen atom than in the original assignment. As a result of this change, the ligand forms additional hydrogen bonding with nearby protein residues—illustrating how a seemingly small change can alter the molecule’s interactions with its protein environment.

Using this model to more accurately identify a tautomer for drug discovery could not only help determine how it fits into a protein binding site but could also improve subsequent computer simulations. When assessing drug candidates, molecular dynamics simulations follow a molecule and its protein target to see how they interact and move over time.

“These calculations require the molecule’s hydrogen positions and chemical bonding to be correctly assigned, and using the wrong tautomer could alter the predicted interactions and dynamics,” said Zhang.

The team also showed that in one test, their open-source tool Tautomer-Predictor, processed the 4.6 million compound Enamine collection in 3.2 hours on a single GPU-enabled node. “Together, these results establish crystallographic proton placement as a rich and underexploited source of chemical knowledge for learning tautomer stability, and provide a practical route to large-scale tautomer assignment for molecular discovery,” the authors concluded.

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Now, researchers have formulated a more effective slow-release injectable drug delivery system that achieved pain-numbing anesthetic effects lasting two to three weeks in rats compared to a commercial formulation lasting about four to eight hours. Because nerve blocks in humans tend to work longer than in rats, this advancement could blow the effective time of currently used anesthetics out of the water and have implications for other types of pain.

This work is published in Nature Biomedical Engineering in the paper, “Ultra-slow release of hydrophilic drugs via multilamellar–multivesicular liposomes formed by unsaturated phospholipids.“

Liposome composition determines how fast drugs leak out, with faster leaking leading to a more potent drug effect over a shorter time period with potentially more toxicity. Up until now, researchers believed that molecules leaked fastest from liposomes made of more “fluid” lipids. However, Yuan Wang, PhD, a research engineer in the laboratory of Daniel Kohane, MD, PhD, challenged this theory by showing that liposomes made of more fluid lipids release drugs that mix well with or dissolve in water, known as “hydrophilic” drugs, extremely slowly. One way to make lipids more fluid is by adding many double chemical bonds to their tails so that the lipids can’t pack together as tightly.

The team demonstrated that the liposomes with many double bonds had a structure with multiple compartments, while those without had a simple spherical structure. As a result, in liposomes with many double bonds, hydrophilic drugs had more lipid barriers to cross leading to slower drug release.

“The more fluid membranes in liposomes with many double bonds may be easier to cross, but the greater number of barriers slow down the drug’s release,” says Wang. “The more fluid liposomes with more double bonds may form concentric spheres that are like onions with many layers or could even potentially be even spheres within spheres.”

Knowing a hydrophilic drug will leak slower from a more fluid liposome, the researchers tested out a proof-of-principle experiment. The team filled their more fluid liposomes with potent tetrodotoxin—a powerful neurotoxin found in pufferfish and blue-ringed octopuses that serves as a powerful numbing agent. When injected near a nerve in the leg of rats, they showed very prolonged local anesthesia, but no toxicity at the injection site or throughout the body. This means the drug released slowly enough to be cleared by the body, but still at high enough levels to be an effective anesthetic. Tetrodotoxin isn’t commercially used in patients yet but could one day be developed as a therapeutic.

“This extended-release combination could be used for longer term perioperative pain instead of opioids, and we are starting to consider using these potentially for chronic pain, as well,” says Kohane, senior associate in pediatric critical care at Boston Children’s and director of Laboratory for Biomaterials and Drug Delivery. “These liposomes can also provide slow release of a wide range of hydrophilic molecules.”

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This multi-strategy nonlinear model predictive control (NMPC) system allows biomanufacturers to switch seamlessly between such objectives as stable operation and economic optimization, according to Mahshad Valipour, PhD, senior research scientist, and Christopher McCready, head of product innovation, both of Sartorius, writing in a recent paper. The control system also accounts for unknown states—many of which are rarely, if ever, measured—through a moving horizontal estimate that considers the process and its constraints.

After the process is stabilized, an economic NMPC (ENMPC) mode further maximizes performance objectives. It does this, Valipour and McCready explain, “by determining optimal operating conditions in real-time… while explicitly enforcing dynamic process feasibility and biological constraints throughout the perfusion run. [It] improves numerical conditioning and avoids instability issues [commonly encountered in standard ENMPC formulations,] eliminating the need for ad hoc damping/terminal functions or frequent weight retuning.”

Combining a multifunction NMPC and an economic mode within one framework enables “seamless transition between operating modes without controller switching or reformulation,” they add. The primary benefit of this approach may be that biomanufacturers can determine maximum feasible operating conditions safely in real time, while accounting for the accumulation of biomaterials that inhibit cell productivity.

The most important step in making this approach work, they indicate, is “capturing the impact of accumulated inhibitory biomaterials on growth and death dynamics.” Conventional models, they point out, do not account for trade-offs among perfusion rate, inhibitor removal, and cell growth. Therefore, conventional models cannot be used to maximize viable cell density.

Experiments using digital twins showed the NMPC transitioned smoothly among process controller strategies while maintaining a healthy cell culture and increasing upstream productivity. Evaluations under realistic real-world conditions showed online and inline measurements of viable cell density and viability matched predictions, as did dead cell density.

Notably, rather than merely maintaining a stable cell culture and viability rate for a prolonged period, this multi-strategy lets biomanufacturers change objectives as the process is running. Even when tested against what they call “a significant plant-model mismatch,” operations, they said, remained stable.

For bioprocessors, this study suggests that advanced automation strategies can resolve the hurdles associated with continuous CHO perfusion, making it more predictable and more efficient.

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Perfusion bioreactors have been a mainstay of the development lab for decades. However, few firms have embraced them at commercial scale, in part, due to concerns about media costs, says Eric Wynne, PhD, a postdoctoral associate at MIT’s electronics research lab.

“While many factors have constrained adoption of perfusion bioreactors, media cost has often been cited as the main issue,” Wynne tells GEN, adding, “We believe recycling has the potential to lower costs as well as the overall volume of media involved in the manufacturing process.”

The idea, detailed in a new study, is to use a process called electrokinetic waste separation to remove cellular debris, reagents, and other potential contaminants from culture media after cultivation.

The approach uses an electric field to split media into a harvest stream that contains uncharged molecules—primarily the nutrients cells need to grow—and a waste stream in which there is a higher concentration of charged molecules, like ammonia and lactate.

“Electrokinetic waste separation provides a way of cleaning media thoroughly before recycling it. This process is what differentiates our work from previous groups that recycled media directly.

“In this work we improve the yield of this process by taking the ‘waste’ stream and processing it again to harvest additional media,” Wynne says.

The aim is to allow manufacturers to reuse a greater proportion of media—in studies, Wynne and colleagues have recovered 87.5% of spent volume—in subsequent culturing processes.

“The advantage is that, by separating waste, you can replace greater quantities of fresh media with recycled media without significantly impacting cell growth or productivity.

“Companies that use perfusion technologies already recycle media. However, typically the volume of reused media is less than 50%. Also, without a cleaning step, the reused media can negatively impact cellular growth and productivity.

“Electrokinetic waste separation has the potential to both increase the amount recycled and reduce any negative impact on productivity,” he adds.

The approach is still at a pilot stage, but the cost-saving potential is significant, particularly in combination with hybrid and fully continuous-mode manufacturing processes, Wynne says.

“More development is necessary before the technology is ready for adoption, particularly in the area of characterizing how media recycling does or does not affect product quality attributes.

“Adoption would likely require more testing at small scale and pilot scale perfusion bioreactors. Additionally, recycling and waste separation would likely be best suited for a fully continuous mAb production process with continuous chromatography downstream,” he says.

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“Scientific possibility alone does not create patient access,” Seyf says.

That distinction sits at the heart of Act for Hope, a not-for-profit, member-led initiative created to accelerate growth across the CGT industry through collaboration. Seyf argues that advanced therapies demand a fundamentally different model from conventional pharmaceuticals because their delivery depends on a tightly connected chain of stakeholders.

From patient identification and starting-material collection through manufacturing, testing, release, logistics, treatment, and long-term follow-up, CGT can involve hospitals, manufacturers, contract development and manufacturing organizations, technology suppliers, regulators, payers, academics, and patients.

“No single organization controls that entire journey,” Seyf says. “That makes collaboration not simply desirable, but foundational.”

While the industry frequently discusses expanding manufacturing capacity, Seyf believes another capability must scale alongside it: collaboration. Shared standards, interoperable digital systems, responsible data exchange, and greater alignment between organizations could become increasingly important as more therapies progress toward commercialization and wider patient populations.

“A therapy may be developed by one organization, but access can only be delivered by an ecosystem,” he adds. “Collaboration has to become infrastructure rather than aspiration.”

Fragmentation carries a hidden cost

One obstacle is that CGT’s rapid development has also produced a highly fragmented operating environment. Companies and institutions have built their own processes, terminology, data structures, and technology platforms—often for sound individual reasons. Collectively, however, those differences can create duplicated work, manual handoffs, disconnected systems, and repeated attempts to solve similar problems.

At relatively low treatment volumes, those inefficiencies might be manageable. At global scale, Seyf says, they risk becoming barriers to patient access by increasing cost, complexity, and time.

The challenge is not to standardize the underlying science, he stresses. Rather, the opportunity lies in harmonizing interfaces and processes where differentiation provides little competitive value.

“The industry has historically been exceptionally good at protecting intellectual property and competing on innovation,” Seyf says. “The next phase requires us to become equally good at identifying the areas where we should not compete.”

Act for Hope aims to provide a neutral setting for that work. Its focus includes standardization, digitization, implementation tools, and responsible, permissioned benchmarking, bringing organizations together to address common bottlenecks without compromising proprietary technologies or intellectual property.

“Collaboration should not mean giving away competitive advantage,” Seyf adds. “It should mean collectively removing the inefficiencies that provide no competitive advantage to anyone.”

Connecting innovation with patients

Two planned projects illustrate that approach. Act for Hope is developing a clinical-trial portal intended to make advanced therapy trials easier to discover and navigate. Despite rapid global innovation, Seyf says, connecting potentially eligible patients with trials remains unnecessarily complicated. A second project, the initiatives hub, is a patient-access portal intended to improve connections among stakeholders involved in moving therapies from scientific development to treatment. Both projects reflect a broader premise: increasing manufacturing output alone will not solve CGT’s access challenge.

“The first chapter of CGT was about proving that the science could work,” Seyf says. “The next chapter must be about proving that the ecosystem can work at scale.”

Technology, automation, and artificial intelligence are likely to play major roles in that transition, but Seyf cautions that technology cannot resolve organizational fragmentation by itself.

“Technology can connect systems. Collaboration connects people, organizations, and purpose,” he adds. “We need both.”

For Seyf, the ultimate benchmark is therefore not the number of therapies approved, facilities constructed, or technologies deployed. It is whether the expanding CGT ecosystem can translate those advances into treatment for the patients who need them. That, he argues, will make collaboration not a supporting feature of CGT’s next era, but one of its defining pieces of infrastructure.

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According to Whitford, who is the founder of Oamaru BioSystems, digital shadows are like digital twins in being real-time digital copies of a process or piece of equipment. Unlike them, however, they aren’t designed to actively control a process. Instead, they simply report back on what’s going on.

This makes them easier to set up than digital twins, he says. “They’re not as comprehensive [as a digital twin], but that might be all you need if you don’t want active control for regulatory reasons.”

Nonetheless, he believes digital shadows are valuable for managing the large, complex datasets being generated by today’s bioprocess analytics. “Machine learning can handle the complexity, the amount, the nonlinearity and high dimensionality of the data we’re getting,” he says.

Such data can include time series, imaging and analytical data, as well as historical data collected during process development.

“For example, you might take the outgassing of a [bio]reactor, look at carbon dioxide and oxygen levels and, from there, infer the metabolic activity,” he says. “And [if you add the historical data] you can infer the number of viable cells.”

By contrast, he says, more simple analytics, such as an equation or simple algorithm, can’t digest the variety of data coming in.

The digital shadow, he says, can make inferences or future predictions by simultaneously integrating process measurements, analytical results, biological observations, historical manufacturing data, and contextual production information. This, in turn, can help manufacturers get more product per square foot of plant, per unit of bioreactor volume or time, he says, and thus aid process intensification.

“Once you’ve defined that goal for your process intensification, you want to know what tools are out there and I want people to know about the tools we have,” he says.

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Basecamp, a frontier AI company focused on therapeutic design, focuses on leveraging EDEN (short for “environmentally-derived evolutionary network), its biological foundation model, to develop in vivo cell therapies designed to reprogram a patient’s cells inside the body.

EDEN is Basecamp’s new class of foundation models trained on what the company says is the world’s largest and most diverse evolutionary dataset. According to Basecamp, EDEN offers the ability to design long and complex DNA sequences with large serine recombinases capable of delivering those sequences precisely.

EDEN-designed cell therapies are also designed to overcome the high manufacturing cost and limited complexity of present-day cell therapies. As a result, Basecamp said in its announcement, its EDEN-designed therapeutics offer the potential to treat complex diseases that include cancer and autoimmune disease, aiming “to underpin the future of cell therapies, making them more sophisticated, more customizable and simpler to administer” than current cell therapies.

“We believe the future of medicine lies in reprogramming the body to repair itself. We design the models and the medicines to teach it how,” Glen Gowers, PhD, Basecamp’s co-founder and CEO, said in the statement. Gowers co-founded Basecamp with Oliver Vince, PhD.

Basecamp says it has shown strong preclinical results across multiple modalities and disease areas. Aiming to expand its partnerships with biopharmas, Basecamp in April appointed Richard Pearce as chief business officer. Pearce previously served as Biogen’s head of business development, strategy, and portfolio management.

“AI-based approaches promise to change what’s possible for patients who currently have few alternatives. This funding brings this technology closer to those who need it most,” Gowers added.

Big-name investors

One big-name investor participating in the financing is Anthropic—the AI model builder behind the Claude family of large language models. Anthropic invested in Basecamp through its Anthology Fund, a $100 million fund launched in 2024 and financed by Silicon Valley-based VC firm Menlo Ventures. Startups financed by the Anthology Fund receive access to Anthropic products and research, $25,000 in free credits towards Anthropic’s most advanced models, and what the company calls “best-in-class” venture support from Menlo.

“We’re particularly interested in ventures that leverage AI to enhance human capabilities and productivity in fields such as healthcare, legal services, education, energy, infrastructure, and scientific research,” Daniela Amodei, Anthropic’s co-founder and president, stated in announcing the launch of the Anthology Fund.

Anthropic’s offerings include Claude Science, the AI research workbench launched in June and featuring Basecamp’s antibiotic design and vaccine prediction AI models.

Another name investor is NVentures, the venture capital arm of Nvidia—the Silicon Valley microprocessing giant with which Basecamp has leveraged AI to unlock programmable gene insertion, which places large therapeutic DNA sequences at precise locations in the human genome.

Researchers from Nvidia joined partners from Basecamp, Microsoft, and two research institutions in detailing EDEN in a preprint posted January 12 on bioRxiv.

63% hit rate

The investigators showed EDEN to achieve an overall functional hit rate of 63.2% across diverse DNA prompts when prompted on only 30bp of DNA from outside the training data. Half (50%) of EDEN-generated LSRs were active in human cells, achieving therapeutically relevant levels of chimeric antigen receptor (CAR) insertion in primary human T cells. Also, an EDEN-generated synthetic microbiome was shown in the preprint to cover 9,067 species with a biome-specific taxonomic accuracy of 99%.

Nvidia and Anthropic were among partners of Basecamp that built its Trillion Gene Atlas, which draws on biological data collected through access and benefit-sharing partnerships in more than 30 countries across all seven continents. The Atlas is at the center of Basecamp’s AI platform, and according to the company is the world’s largest proprietary biological AI training dataset. Pacific Biosciences of California (PacBio) and Ultima Genomics also partnered in building the Atlas.

Trained on data from the Atlas, Basecamp’s EDEN models deliver a universal understanding of how DNA works across all of life. Its capabilities include designing cell and gene therapies, enzymes and peptides.

Unlike AI systems developed for a single scientific task, EDEN models are trained to recognize patterns across biology. As a result, it can generate potential therapeutic candidates directly from information about a disease, an approach already demonstrated through Basecamp’s collaboration with Anthropic on Claude Science.

Anthropic and NVentures are among participants in the financing, along with Catalio, European Tech Collective, Firebrand River Capital, King Philanthropies, NATO Innovation Fund, Redalpine, The Rockefeller Foundation, Singular, Sovereign AI, and True Ventures.

‘Next transformation’

Basecamp has garnered additional investment from senior leaders across biopharma and global industry, including André Hoffmann, vice chairman of Roche, a board member of Roche subsidiary Genentech, and co-chair of the World Economic Forum.

“The biotechnology revolution that began fifty years ago transformed how we make medicines. Personalized, AI-designed therapeutics represent the next transformation of that journey,” Hoffmann stated. “Basecamp Research has built the full platform to deliver it, from biological data to trained models to designed therapies. This will be key in helping the industry to continue to innovate.”

Basecamp raised $60 million in Series B financing in 2024, and a $20 million Series A round two years earlier.

The Series C financing was led by S32, a Palo Alto, CA-based venture firm. S32 has about $3.5 billion in assets under management after closing earlier this year on a $517 million sixth flagship fund, according to PitchBook.

As a result of the latest financing, Andy Conrad, General Partner at S32 and former CEO of Google’s Verily, will join Basecamp’s board.

“AI is opening up new possibilities across every part of society, but perhaps nowhere is the potential more meaningful than in human health. The ability to combine AI, biological data and scientific insight could transform how we understand disease, discover medicines and ultimately improve and extend people’s lives,” Conrad stated. “Basecamp Research is building an important technology platform at the center of that opportunity.”

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Artificial intelligence is opening new possibilities for drug discovery. But in neuroscience, AI is only as powerful as the biological data behind it, and BrainStorm Therapeutics believes AI combined with human brain biology can be better.

BrainStorm is generating that biology in the laboratory using patient-derived human brain organoids. These living, three-dimensional models reproduce features of the human brain, generating rich datasets that BrainStorm uses for phenotypic drug discovery and to train AI models.

By combining patient-derived brain organoids with AI, the company aims to uncover disease mechanisms, identify therapeutic targets, screen drug candidates, and determine whether potential treatments can reverse disease-associated dysfunction before they enter clinical trials.

BrainStorm is applying the platform across neurological diseases, with a lead therapeutic program in CDKL5 deficiency disorder, or CDD, and discovery programs in Parkinson’s and Alzheimer’s diseases. The approach also builds on earlier work in Rett syndrome, advancing a repurposed therapeutic candidate from organoid screening to an FDA-cleared Investigational New Drug application for a Phase 2 clinical trial.

The company has attracted attention from the scientific and investment communities, most recently earning the Seed-Stage Start-Up Stadium Award at the 2026 BIO International Convention.

The competition recognizes two companies selected by investor judges from approximately 50 presenting start-ups. BrainStorm received the Seed-Stage Award for companies that had raised less than $1 million, while NF1-focused iNFixion Bioscience received the Emerging Company Award for companies that had raised between $1 million and $10 million.

The brain power behind the platform

BrainStorm generates three-dimensional brain organoids from induced pluripotent stem cells derived from patients carrying disease-causing mutations. The cells are differentiated into regionally defined brain organoids containing multiple interacting neural cell types and functional synaptic networks.

Although organoids do not reproduce an entire human brain, they can model selected cellular, molecular, and functional features of specific human brain regions that are difficult to capture in conventional cell cultures or animal models.

“When we measure calcium signaling and electrophysiological activity in these brain organoids, we can detect patterns of neuronal and network dysfunction associated with specific neurological disorders,” said Maya Gosztyla, Ph.D., BrainStorm’s co-founder and chief scientific officer. “These models bring us closer to studying human disease biology in the laboratory and give us a powerful system for evaluating whether a potential therapy can correct that disease biology.”

BrainStorm uses organoid data to investigate disease mechanisms, identify therapeutic targets, screen drug candidates, and determine whether treatments reverse disease-associated phenotypes. Those experiments also generate proprietary, human-relevant datasets to train and refine the company’s AI models.

“This allows us to do two things at once,” Gosztyla said. “We can directly test whether a potential therapy rescues a disease phenotype while generating rich, high-quality human datasets that improve our AI models.”

BrainStorm uses those data to identify disease-associated gene networks and potential therapeutic targets, then brings AI-generated hypotheses back into its organoid platform for experimental testing.

“That creates a closed loop between computation and experiment,” Gosztyla said. “By grounding our AI models in patient-derived human biology and then experimentally testing their predictions, we believe we can improve the likelihood that discoveries made in the laboratory will translate into meaningful benefits for patients.”

Platform validation in Rett syndrome

BrainStorm’s strategy builds on work led by founder and CEO Robert T. Fremeau, Jr., Ph.D., while he was chief scientific officer of Vyant Bio. Using patient-derived brain organoids, the Vyant team identified repurposed drug candidates for Rett syndrome and a novel therapeutic target and small-molecule hit scaffold for CDD. Rett syndrome is a rare genetic neurological disorder that primarily affects girls and can cause developmental regression, impaired communication and movement, seizures, and other serious symptoms.

“Our most clinically advanced proof point originated from work I led as chief scientific officer of Vyant Bio,” Fremeau said. “Working with the International Rett Syndrome Foundation, we used patient-derived brain organoids to conduct phenotypic screening and identified donepezil as a potential repurposed therapy for Rett syndrome.”

Donepezil is FDA-approved for Alzheimer’s disease but not for Rett syndrome. The program progressed from organoid screening to submission of a Phase 2 clinical trial application in approximately nine months. The FDA subsequently cleared the Investigational New Drug application, allowing the Phase 2 program to proceed. The translational package included efficacy evidence generated in patient-derived human brain organoids, without requiring new animal efficacy studies for the repurposed drug.

“To our knowledge, donepezil represents the first therapeutic candidate identified through phenotypic screening in a patient-derived brain organoid to progress to an FDA-cleared IND,” Fremeau said. “For us, that provided important translational and regulatory validation of the organoid-based approach demonstrating that human brain organoids can move beyond disease modeling to become a practical drug-discovery platform capable of generating therapeutic hypotheses that advance toward the clinic.”

The lead program: CDKL5 deficiency disorder

While the Rett program provided an important example of clinical translation, CDD is now the focus of BrainStorm’s therapeutic development efforts.

CDD is a rare developmental and epileptic encephalopathy caused by pathogenic variants in the CDKL5 gene. It typically presents in early infancy with severe, treatment-resistant seizures and profound developmental, motor, communication, and visual impairments. Existing treatments can reduce seizures in some patients, but no approved therapy addresses the underlying disease biology and neurodevelopmental impairments.

One challenge in developing therapies for CDD is the disorder’s genetic diversity. Different patients carry different pathogenic variants in CDKL5, raising an important question for drug discovery: Can a treatment correct disease biology across multiple genetic backgrounds?

To address that question, BrainStorm is working with the CURE5 Foundation, a patient-led CDD organization, to develop patient-derived brain organoid models representing multiple pathogenic CDKL5 variants.

“We’re growing several new stem-cell-derived brain organoid models from patients with different types of CDKL5 mutations,” Gosztyla said. “These models allow us to ask whether a therapy can work across the genetic diversity of CDD.”

The models provide BrainStorm with a genetically diverse human platform for studying CDD biology and evaluating therapeutic response. They can also support systematic screening of approved drugs to identify potential repurposing opportunities for patients.

At the same time, BrainStorm is advancing its own proprietary therapeutic program for CDD. The program builds on a novel therapeutic target and small-molecule hit scaffold originally identified through phenotypic screening in patient-derived CDD brain organoids.

“Our goal is to develop a first-in-class, disease-modifying therapy that addresses the underlying neuronal dysfunction rather than only treating the symptoms,” Gosztyla said.

CDD organoids exhibit reproducible hyperexcitability that can be measured using high-throughput calcium imaging and electrophysiology. BrainStorm’s hit compound reverses aspects of this disease-associated neuronal dysfunction in CDD organoids while showing little or no effect in healthy controls, suggesting disease-state-selective activity.

The company is now validating the therapeutic response across multiple patient genotypes while advancing the chemistry through hit-to-lead optimization toward selection of a development candidate.

Together, the CURE5 collaboration and BrainStorm’s proprietary program are designed to answer complementary questions: whether existing medicines can be repurposed for genetically diverse CDD patients, and whether a new disease-modifying therapy can be developed specifically to correct the disorder’s underlying neuronal dysfunction.

Advancing toward a development candidate

BrainStorm is now raising a seed financing round to advance its CDD program through hit-to-lead optimization toward a development candidate and expand its therapeutic pipeline.

“The main focus of our current fundraising is to bring the CDD program forward toward a development candidate,” Gosztyla said.

The company has attracted more than $1 million in non-dilutive support. A Phase I Small Business Innovation Research award from the National Science Foundation supported development of BrainStorm’s AI foundation-model capabilities and Parkinson’s disease research, including identifying potential disease-modifying targets.

BrainStorm is also collaborating with Novoron Bioscience and Defined Bioscience on a National Institute on Aging Direct-to-Phase II SBIR award. The project uses three-dimensional cortical organoids to model pathological prion-like tau propagation and identify potential treatments for Alzheimer’s disease.

The company has received recognition from organizations including California Life Sciences, NVIDIA, BioMarin, and Servier. BrainStorm has also entered a master collaboration agreement with BioSymetrics, part of Lunai Bioworks (NASDAQ LNAI), to support translational validation.

Its latest recognition, the BIO Start-Up Stadium Award, came after BrainStorm presented at the 2026 BIO International Convention.

Along with exposure to biotechnology investors, the award includes participation in the Science Inc. Accelerator operated by The Innovation Space.

“The accelerator has been extremely valuable in helping us address the practical steps required to move from early therapeutic discovery through development, regulatory strategy, and financing,” Gosztyla said.

The Start-Up Stadium competition also provided BrainStorm with exposure to investors, including members of the judging panel.

“Winning the Seed-Stage Start-Up Stadium Award provides important external validation of our science, our team, and our opportunity to build a differentiated CNS therapeutics company,” Fremeau said. “We are currently raising our seed round to advance our lead CDD program toward a development candidate and demonstrate that patient-derived human brain models can help identify therapies with a greater likelihood of translating into meaningful benefit for patients with devastating neurological diseases.”

After all, developing new neurotherapeutics requires money—and brains.

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The work, described in the paper titled “Biomimetic graphitic carbon nitride nanoparticles for multiscale photomodulation and therapeutic intervention,” was published in Nature Biomedical Engineering. The international team was led by Menglin Chen, PhD, at Aarhus University, with collaborators from the University of Chicago, the University of Eastern Finland, Aarhus University Hospital, and the University of Copenhagen.

The study addresses a central challenge in retinal degeneration: even after light-sensitive photoreceptors are lost, other retinal neurons can persist. The researchers aimed to create a wireless interface between light and those remaining cells without relying on mutation-specific gene therapy, optogenetic modification, or surgically implanted electronics.

“When we started, our fundamental question was whether we could create a material that could act as a wireless interface between light and living cells,” said Chen, who is an associate professor at the Department of Biological and Chemical Engineering. “We can now see that the particles are able to activate nerve cells in blind retinas. That brings us closer to our long-term goal of developing a new type of retinal prosthesis.”

The retinal experiments moved the platform toward a more specific therapeutic application. After the nanoparticles were injected into mouse eyes with advanced retinitis pigmentosa, they accumulated near retinal ganglion cells, which help relay visual information from the eye to the brain. When the eyes were illuminated, the team detected light-induced activity in the visual cortex and observed behavioral responses to light. The researchers also showed that the nanoparticles could activate retinal ganglion cells in isolated porcine retinal tissue under LED photostimulation.

The findings do not show restored normal vision, but they suggest a possible route for restoring light sensitivity in retinas where photoreceptors have degenerated. “Instead of genetically modifying these cells, we use the nanoparticles to create a new connection between light and the nerve cells,” Chen said. “In this way, we are trying to make a blind retina respond to light again.”

The next steps are substantial. The team will need to refine delivery, assess how long the nanoparticles remain functional in the eye, study their long-term safety, and determine whether the light-evoked responses can be strengthened and controlled in ways that are useful for vision restoration.

For now, the work marks an early but notable step: a biomimetic material that can translate light into biological signals across scales, from individual cells to degenerated retinal tissue. Whether that microscopic “solar cell” concept can ultimately help people with vision loss will depend on the next phase of preclinical development.

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In an advance that could lead to better ways to diagnose and treat those diseases, MIT researchers have developed a noninvasive way to detect biomarkers of senescence. Their method is based on Raman microscopy, which can reveal the biochemical composition of cells without harming them.

Using the new technique, “RamanOmics”, which combines Raman microscopy with gene expression data at single-cell resolution from the same cells, the researchers were able to identify unique “barcodes” that can be used to quickly identify senescent cells. And while their reported study was carried out in mouse cells, the scientists are now working on adapting it for use with human tissue.

“You can imagine that one day we may develop an endoscope that can look inside your body and identify cellular senescence,” says Jeon Woong Kang, PhD, an MIT research scientist and co-senior author of the team’s published study in Nature Aging, titled “RamanOmics decodes the spatial vibrational–molecular architecture of senescence in aging and repair,” in which they concluded, “Together, RamanOmics provides a tissue-agnostic framework for scalable, multimodal profiling of cellular states.”

The paper’s co-senior authors are Peter So, PhD, director of the MIT Laser Biomedical Research Center (LBCR) and an MIT professor of biological engineering and mechanical engineering, and Jian Shu, PhD, an assistant professor at Massachusetts General Hospital (MGH) and Harvard Medical School, and an associate member of the Broad Institute and Ragon Institute. The research is part of a National Institutes of Health initiative called the Cellular Senescence Network, which is pursuing a deeper understanding of senescence in hopes of developing therapies that could combat some of the tissue-damaging effects of senescent cells.

Cell senescence is often triggered by DNA damage, which leads to an irreversible arrest of the cell cycle. These cells don’t die, but they undergo significant changes to their shape, metabolic processes, and gene expression profiles.

The immune system is responsible for clearing out these “zombie cells,” but as people age, this clearing process becomes less efficient. When senescent cells accumulate, they may contribute to sagging skin, muscle weakness, and chronic conditions such as osteoarthritis and type 2 diabetes (T2D).

Cellular senescence also has beneficial effects, playing critical roles in embryonic development and tissue regeneration. “Senescence is not just a pathological condition,” So said. “The idea behind the NIH Cellular Senescence Network is to take a very comprehensive approach to understand senescence and identify senescent cells, because it plays a role in so many normal physiological conditions and many pathological conditions.”

Scientists have already identified a few biomarkers for senescence, including two proteins, p16 and p21, which are involved in halting the cell cycle. However, those proteins can only be identified using a process that ends up destroying the cells. “Aging reshapes tissues through the accumulation of senescent cells, yet current definitions of senescence still depend largely on transcriptomic or histological markers that fail to capture its underlying biochemical remodeling,” the team further pointed out.

The MIT team wanted to find a way to noninvasively identify senescent cells using Raman microscopy. Unlike RNA-sequencing, which consumes the cells as it analyzes them, Raman microscopy is a nondestructive technique that reveals the chemical composition of tissues or cells by shining near-infrared or visible light on them.

For their newly reported study the researchers used Raman microscopy in conjunction with spatial RNA sequencing—a technique that reveals where genes are active within a tissue—to identify new markers of senescence. By combining these two techniques the team was able to generate a much broader picture of the distinctive features of senescent cells, including gene expression levels, spatial location, and other biochemical information.

“Our idea was to look at many different features to characterize senescence,” Shu noted. “That’s why we wanted to combine both single-cell gene expression and Raman microscopy, so that we can characterize the senescence from two complementary views.”

Using both methods of analysis, the researchers examined skin and lung tissue from 2-month-old mice and from 26-month-old mice. One of the most dramatic changes seen in both lung and skin cells was an increase in lipid synthesis in older cells, along with accumulation of lipids. How this affects the physiology of the cells is not yet known, the researchers say.

They also found some effects that were specific to each tissue. In senescent skin cells it was discovered that cellular pathways associated with muscle contraction and with remodeling of collagen and the extracellular matrix (ECM) were significantly affected. And in aged lung tissue, there was increased activity of genes involved in immune activation and inflammation. “Together, these results reveal tissue-specific aging patterns: immune activation and vascular remodeling with diminished epithelial renewal in lung, versus metabolic decline and impaired ion homeostasis with partial preservation of epithelial programs in skin,” they stated. In future work, the researchers hope to study further what role these changes play in senescent cells.

Using these data, the researchers were able to identify combinations of Raman peaks that correlate with senescence. These peaks, which represent specific chemical bonds, are linked to the presence of certain lipids, proteins, or other molecules.

“Combining the most important Raman features with the most important gene signatures, we were able to create a barcode that can help us to identify senescent cells in a more unbiased way,” commented Salvatore Sorrentino, PhD, a postdoc at MIT and study co-first author. “Using this barcode, we can focus on a few Raman bands that emerged as the most informative in this work.” Using these bands, it could be possible to identify senescent cells by looking for just those bands of the Raman spectrum. This could help to enable diagnostics that would detect cells that have become senescent.

“Nondestructive Raman features alone could serve as biomarkers of senescence, enabling in vivo monitoring of tissue aging or evaluation of senolytic therapies in humans,” the authors stated. “Coupling biochemical readouts with transcriptomic programs also opens opportunities for high-throughput screening of lipid-pathway modulators and longitudinal tracking of senescence in translational contexts such as skin aging, fibrosis or wound repair.”

To help make that possible, the researchers are now working on a higher-speed version of their Raman imaging system. Currently, it takes about 30 hours to analyze a tissue sample about one square millimeter in size, but they hope to develop a system that can quickly pick out the Raman barcodes they identified from larger samples.

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“Our collaboration with Bristol Myers Squibb, which now spans more than 25 years, is anchored in scientific excellence, operational reliability, and a shared commitment to advancing innovative therapies,” said Peter Bains, managing director and CEO of Syngene.

“The agreement to extend this partnership through 2035 enables us to plan together for the future in terms of building new capabilities and infrastructure with a decade long horizon. Taking a long-term perspective is a key feature of our partnership which adds strategic value to both companies.”

“At Bristol Myers Squibb, everything we do begins with patients. We greatly value our long-standing partnership with Syngene, which has been instrumental in advancing our scientific ambitions,” added Payal Sheth, senior vice president, therapeutic discovery sciences, Bristol Myers Squibb.

“This expanded collaboration reflects our commitment to advancing innovative science by effective integration of our research, development, and manufacturing capabilities to accelerate the delivery of transformative medicines and bring hope to patients around the world who are waiting for new treatment options.”

The collaboration between Syngene and Bristol Myers Squibb began in 1998, culminating in the establishment of the Biocon Bristol Myers Squibb Research and Development Center (BBRC), Syngene’s first dedicated R&D Center, which was fully commissioned in 2009. Bains noted that the BBRC has evolved into a major strategic R&D site for Bristol Myers Squibb.

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However, the integrity of western blot data has come under scrutiny in recent years following the retraction of a number of papers due to image irregularities. To that end, many major journals, including the Journal of Biological Chemistry, Cell, and Nature have specific submission guidelines, with data quality and transparency being top priorities. With this in mind, it is crucial for researchers to understand where to draw the line between improving image presentation and data manipulation when it comes to western blotting.

Understanding data misrepresentation through image manipulation

Western blot image integrity can be compromised through undisclosed, seemingly minor adjustments to the contrast, brightness, and exposure through to more deliberate edits, such as cropping out or duplicating bands or lanes, combining lanes from different gels, or rotating bands. While many of these practices can be performed inadvertently, they can mislead data interpretation.

For presentation purposes, non-destructive adjustments, such as image transformation and background subtraction are reasonable and often scientifically necessary depending on sample complexity and signal specificity. However, these adjustments must be made consistently across all lanes being analyzed and must be fully disclosed in figure legends or methods.

There are several image analysis software packages available to researchers to aid gel image analysis and quantitation. These include ImageJ, developed by the National Institutes of Health, which is widely accepted by many journals. The software preserves image data and allows creation of macros, enabling identical processing to be applied across multiple images. ImageJ quantifies signal intensity directly, so it’s suitable for a range of workflows including total protein normalization from stain-free approaches or stained images.

As with any densitometry tool, quantitation should be performed on raw images within the linear range of detection, and macros should be validated against a known standard to confirm they produce accurate, reproducible results across all images in a set. Fiji is an image processing package that facilitates analysis in ImageJ, offering integration and comprehensive documentation, and is recommended for first-time users.

Beyond this widely used option, a number of other tools serve more specific purposes, from general image editing to acquisition-integrated workflows. GNU Image Manipulation Program (GIMP), Python with scikit-image, EBImage, and Image Lab are also available to researchers and offer various capabilities:

• GIMP: GIMP is not designed for scientific quantitation but offers general-purpose image editing for cropping, documentation and annotation.
• Python with scikit-image: For researchers with programming expertise, Python with scikit-image provides full control over imaging processing pipelines.
• EBImage: Hosted within the Bioconductor Project, EBImage allows seamless integration with downstream statistical analysis using R programming.
• Image Lab: The software preserves the full context of data from acquisition through analysis within a secure traceable environment, enabling documentation and transparency of image generation and processing.

Choosing the most reliable normalization method

Alongside the choice of analysis software, reliable protein quantitation also depends on the normalization strategy used to correct for any non-biological differences between test samples prior to comparison, and the choice of method has direct implications for data integrity.

Single “Housekeeping” Protein Normalization. Traditionally, western blots have been quantified via normalization against a single loading control, typically housekeeping proteins (HKPs) such as GAPDH, β-actin or β-tubulin, which are ubiquitous, abundant and assumed to be consistently expressed. This approach is widely used, however, HKPs must be validated against positive and negative controls within the researcher’s specific experimental context to confirm consistent expression levels across samples.

As HKP expression is often considerably higher than that of target proteins, rigorous linear range determination must be established to avoid oversaturation and loss of quantitative accuracy. This process often requires several rounds of optimization of primary and secondary antibody dilution ratios, which can add significant time and complexity to the experiment.

Despite HKPs’ ubiquitous expression, their expression levels have been shown to fluctuate across different cell types, cell states, and disease states, including in cancer. Therefore, it is critical for researchers to validate their HKPs for consistent expression across different sample types and experimental conditions.

Normalizing western blots using a single loading control may require stripping and reprobing of the membrane to detect both target and control signals if the proteins run at similar molecular weights. This process can introduce variability and the potential for incomplete stripping or uneven reprobing, increasing the risk of signal variation and reducing result reliability.

Total Protein Normalization. Total protein normalization (TPN) overcomes both the linearity challenges of immunodetection and the reliance on a single control protein to represent the entire protein population (Table 1). Instead, TPN quantifies the total protein loaded in each lane, measured by collecting the signal on the membrane, to produce a normalization factor that is comprehensive and inherently stable. This can be achieved using Stain-Free technology or reversible staining methods such as Ponceau S.

One study compared the accuracy and precision of normalization of three HKPs (β-tubulin, actin and GAPDH) against Stain-Free TPN. Although β-tubulin and actin showed accuracy comparable to that of Stain-Free TPN, they exhibited lower precision, potentially reducing the reliability of the measurements. At the same time, GAPDH plateaued rapidly due to oversaturation, resulting in poor accuracy.

Another study reported similar findings by comparing the linearity of a series of dilutions obtained by Stain-Free TPN measurement as well as HKPs immunodetection, further demonstrating that Stain-Free TPN can serve as a more reliable and accurate loading control than HKPs (Figure 1).

Stain-Free TPN methods were introduced to address variation in membrane sensitivity, allowing the gel and blot to be visualized through an imaging step that does not interfere with downstream immunodetection. This is particularly useful for enhancing data integrity as Stain-Free approaches provide a true scalar relationship between loading amount and signal intensity, so both target and loading signals can be quantified accurately within a linear dynamic range by normalizing each band to the total protein in each lane. This approach improves the reproducibility of TPN, and was recently shown to reduce variability compared to actin or β-tubulin normalization while also reducing the sample size needed for statistical significance by >50%.

However, researchers should be aware that since TPN reflects the whole protein population, it can obscure treatment-induced global shifts in protein expression, so the normalization approach chosen should be matched to the biological context of the experiment.

Upholding data integrity. A western blot’s quantitative reliability is dependent on the decisions made at every stage, from image acquisition and processing through to the normalization strategy applied. Rigorous documentation is essential for the transparency and integrity of published data but does not negate the other steps needed to ensure biological validity and quantitative accuracy. Central to this is the normalization method chosen to account for non-biological differences between samples.

Whichever approach is used, it must be reported and accompanied by an explanation of why it was the most suitable choice for the experiment and its biological context. While there are no fixed requirements on which normalization method researchers should follow, many journals now strongly recommend the use of TPN and stress that HKPs should only be used where there is strong evidence that their expression is unaffected by the experimental conditions.

Together, transparent audit-ready documentation, careful tool selection and a well-justified normalization strategy form the foundation of credible, reproducible western blot data, and meet the growing expectations of journals and the wider research community.

Nikolas Chmiel, PhD, is associate director R&D, life science group, Bio-Rad Laboratories.

The post Best Practices for Establishing Data Integrity in Western Blotting appeared first on GEN - Genetic Engineering and Biotechnology News.

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Thomas Quinn

R&D Group Leader
Takara Bio USA

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Panelist

Thomas Quinn

Thomas Quinn earned a BS in zoology (genetics) from Michigan State University and an MS in molecular medicine and genetics from Wayne State University, where his thesis involved viral vector development for CAR T therapies targeting melanoma and lung cancers. Since 1998, he has led the viral delivery R&D group at Takara Bio USA, focusing on high-efficiency viral delivery systems (adenoviral, retroviral, lentiviral, and AAV) and CRISPR/Cas9 genome editing products.

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Guangping Gao, PhD

Professor and Chair
Dept. of Genetic and Cellular Medicine
UMass Chan Medical School

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Panelist

Guangping Gao, PhD

Guangping Gao, PhD, is an internationally recognized gene therapy researcher who played a key role in the discovery and characterization of a new family of adeno-associated virus (AAV) serotypes, which was instrumental in reviving the gene therapy field. His scientific research career has primarily focused on molecular genetics and viral vector gene therapy of rare genetic diseases, encompassing disease gene cloning, causative mutation identification, pathomechanism investigation, animal modeling, novel viral vector discovery, and engineering for in vivo gene delivery, vector biology, preclinical and clinical gene therapy product development, viral vector manufacturing for preclinical and clinical gene therapy applications as well as technology platforms development as novel approaches for human gene therapy. He has also co-founded several gene therapy companies.

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Technologies for adeno-associated virus (AAV) development are advancing rapidly, driven by innovations in vector engineering and production. New insights into vector quality and performance are supporting the development of new strategies and tools for AAV workflows. These include advances in capsid engineering and workflow standardization—which are accelerating the development of more effective gene therapies.

In this GEN Learning Lab, our expert panelists Guangping Gao, PhD, and Thomas Quinn will explore critical steps in the AAV workflow that influence vector quality and downstream experimental success. The discussion will highlight advances in purification and recovery strategies, followed by approaches for accurate AAV titration and vector characterization to support reproducible research and scalable AAV production. The panelists will also discuss innovations in next-generation AAV designs that are empowering researchers to improve gene delivery performance and expand the potential of gene therapies.

Key takeaways include:

• Practical approaches to overcoming challenges in AAV purification, titration, and downstream analysis
• Best practices for AAV production and workflow standardization
• Emerging technologies that support reproducible and scalable AAV production workflows

Produced with support from:

The post Advancing AAV Development: From Production to Performance appeared first on GEN - Genetic Engineering and Biotechnology News.

As Herb Sarnoff sits in the hospital, waiting for a pain specialist to see his daughter, he describes how a mutation on just one side of the NF1 gene causes neurofibromatosis type 1 (NF1).

“You have one good NF1 gene producing the neurofibromin protein your body needs, and one missing or mutant allele that isn’t, so every cell is not getting enough normal NF1 protein,” he explains. The result is a wide range of difficult symptoms, including painful tumors, bone conditions like scoliosis and osteoporosis, high rates of cancer, and neurocognitive manifestations such as learning disabilities, autism and sleep dysregulation.

Since discovering his daughter’sNF1, a rare disease impacting 1 in 3000 people, nearly 25 years ago, Sarnoff has slowly transformed himself from a tech entrepreneur with limited knowledge of biology to leading iNFixion Bioscience, a biotech developing treatments for NF1. Infixion’s novel NF1 approach aims to supercharge the function of the one good allele rather than trying to fix the mutant one. And the judges were impressed enough to award Infixion a Start-Up Stadium top prize at the 2026 BIO International Convention.

The award recognizes just two start-ups—from among 50 presenting—that investor judges deem to be most promising. iNFixion Bioscience won the Emerging Company Category (between $1 million-$10 million raised). The Seed-Stage winner, with less than $1 million raised, is BrainStorm Therapeutics.

iNFixion’s innovation

Gene therapies often seek to correct mutations, but as Sarnoff explains, “fixing” mutant NF1 genes is difficult. “The gene itself is extremely large: 320,000 base pairs of DNA,” he says, adding that sequencing has identified over 5,000 unique NF1 gene mutations, with no hotspots. “So gene therapy for NF1 is really, really challenging.”

Instead, iNFixion is targeting the healthy allele, increasing the amount of NF1 protein it can produce by blocking microRNAs that modulate protein expression.

“MicroRNAs are basically a feedback loop regulating protein in the body by putting a brake on protein production when necessary,” Sarnoff explains. “If you can block the right microRNAs, you’re essentially taking the brake off. But microRNAs are not specific to one gene. So if you take out a microRNA, you’ll likely have off-target effects.”

Instead of completely blocking the targeted microRNA, iNFixion seeks to block its function exclusively in the NF1 gene.

“The approach being pursued utilizes antisense oligonucleotides (ASOs) that block microRNA binding only on NF1 mRNA. This prevents that microRNA from putting a brake on NF1 protein production,” Sarnoff explains. “But that microRNA is still free to work on other genes, thus limiting potential off-target effects.”

iNFixion has shown in early cellular in vitro experiments that its ASO can boost NF1 protein expression by up to 70-80%. They have also adapted their ASO from the human version to a mouse version and shown they can boost NF1 protein expression in the brains of mice. The next step is to optimize for safety and efficacy in both human NF1 organoids and NF1 animal models.

The drive for funding

As with all start-ups, iNFixion is constantly seeking funding to continue its work. Thus far, most of the work has been funded by the National Institutes of Health (NIH), Department of Defense (DoD), and foundation grants, Sarnoff says.

“We’ve also been fortunate to get lab space at J&J’s San Diego incubator called JLABS,” he says. “It’s a prestigious and collaborative environment for drug discovery start-ups.”

As he seeks future funding, Sarnoff is hopeful of attracting investor interest. One advantage: Even though NF1 is a rare disease it is not that rare, affecting 125,000 Americans and 2.5 million worldwide.

“So it’s a bit of a sweet spot,” he explains. “We get all the benefits of orphan disease, including special treatment at the FDA, access to priority review vouchers and R&D tax incentives, but it’s a big enough market that there’s definitely interest from pharma.”

Sarnoff says iNFixion is in discussions with pharmaceutical companies interested in iNFixion. As for venture capital, Sarnoff notes that few VC’s provide early-stage funding for orphan disease, although a handful of professional investors are showing interest.

Personal motivation

Having explained the disease and Infixion’s approach, Sarnoff begins to grow impatient waiting for his daughter’s pain specialist. Managing pain is a big part of NF1, according to Sarnoff, who says his daughter has had chronic pain for over 10 years related to tumors and bone issues.

His daughter has had 10 major surgeries for scoliosis and tumor removal, and lives with neurocognitive “executive functioning issues,” Sarnoff says. “She’s certainly had her challenges along the way.”

Sarnoff isn’t the only one in his company with personal motivation. Of the seven members in iNFixion’s core team, Sarnoff and three others are NF1 parents, including a pathologist and PhD scientist.

“I made a commitment back in 2017. I said, ‘I’m going to do this.’, and I’ve been working full time on it since,” he says.

An inventor with several patents and previous CEO experience launching a (retail/tech) start-up, Sarnoff is comfortable in the start-up world, but biotech was new.

“I’ve had to start a new career, learning biology and drug discovery, which were completely foreign,” he explains. “I just started gathering resources like any start-up. You begin with an idea and limited resources, and you start building pieces.”

iNFixion is now winning prizes and impressing investors, and Sarnoff clearly seems dedicated to building the other pieces needed for Infixion’s success—and his daughter’s health.

The post iNFixion seeks NF1 treatment by enhancing what the body is doing right appeared first on Bio.News.

A new study from researchers at Gladstone Institutes and the University of California, San Francisco (UCSF), identifies one viral protein, ORF8, as a key driver of that process. The paper, “Secreted ORF8 reprograms macrophages to enhance SARS-CoV-2 infection of lung epithelial cells,” was published in Science Advances.

The work builds on earlier efforts by Gladstone and UCSF scientists to map interactions between SARS-CoV-2 proteins and human proteins in search of viral vulnerabilities that could be targeted with drugs. ORF8 had emerged as an intriguing but puzzling candidate. In isolated lung cells, ORF8 appeared to limit viral replication, yet SARS-CoV-2 variants lacking ORF8 have tended to cause milder disease.

To resolve that contradiction, Melanie Ott, MD, PhD, director of the Gladstone Infectious Disease Institute, and colleagues focused on macrophages, immune cells that help shape the body’s response to infection and inflammation. The team exposed macrophages to ORF8, studied how the cells responded to SARS-CoV-2 infection, and then tested how those immune-cell changes affected nearby alveolar type II lung epithelial cells. They also evaluated ORF8’s effects in mice infected with SARS-CoV-2.

The researchers found that ORF8 increased macrophage expression of angiotensin converting enzyme 2, or ACE2, the receptor SARS-CoV-2 uses to enter cells, making the immune cells more permissive to infection. Once infected, ORF8-exposed macrophages were more likely to lose antiviral function, undergo inflammatory cell death, and release signals that promoted lung inflammation and made surrounding lung epithelial cells more vulnerable to viral replication.

“We were surprised to see how effectively ORF8 turns our own immune defenses against us,” said first author Yusuke Matsui, MD, PhD, a staff research scientist in Ott’s lab. “ORF8 is hijacking macrophages to enhance infection of the surrounding tissue.”

In co-culture experiments, the presence of macrophages changed ORF8’s effect on infection. As the authors wrote in the paper, macrophage co-culture “overrides ORF8’s previously reported inhibition of AT2 [human alveolar type II] infection, restoring infectious viral production.” In mice, SARS-CoV-2 carrying ORF8 caused greater lung inflammation, viral burden, and scarring than virus lacking the protein, supporting the idea that ORF8 helps create a feedforward circuit linking immune-cell infection to lung pathology.

The work also highlights a potential therapeutic target. Researchers tested brodalumab, an antibody already FDA-approved for psoriasis that blocks IL-17RA, the receptor previously linked to ORF8. In mice, IL-17RA blockade countered “ORF8 activity, lowering viral burden and attenuating pulmonary inflammation and fibrosis,” the authors wrote. Ott said the findings could support more targeted treatments for severe COVID-19. “By showing that this single viral protein is the main bridge between viral growth and tissue damage, we’ve found a clear target for new treatments,” she added.

The post SARS-CoV-2 Protein Fuels Lung Inflammation by Hijacking Macrophages appeared first on GEN - Genetic Engineering and Biotechnology News.

Both flatworm and human brains are made up of networks of neurons that communicate with each other by sending electrical or chemical signals. Some neurons react to stimuli, such as light or touch, while others control movement. Flatworms can use stem cells to replace neurons after injury. But while humans also have stem cells, they are unable to transform into new neurons effectively enough to heal injury.

The new study sheds light on how shared genes work in flatworms and lays the groundwork for researchers to investigate similar pathways that might be activated in humans to design better therapies for traumatic brain injuries or diseases.

Rachel Roberts-Galbraith, PhD, associate professor in UGA’s Franklin College of Arts and Sciences, said, “Big picture: We would like to come up with ideas for how to better empower the human brain to regenerate itself. The understanding of brain regeneration that we can develop using simple animals gives us a reason to be optimistic. It’s not an inherent property of brains that makes them bad at regeneration. It’s something specific to humans.”

Roberts-Galbraith is senior and corresponding author, and Kendall Clay, PhD, and Taylor Medlock-Lanier, PhD, are co-first authors of the team’s study, titled “Combinatorial mechanisms specify cellular location and neurotransmitter identity during planarian neurogenesis.” In their paper the team concluded “Our work suggests that combinatorial instruction of cell type and spatial identity could improve exogenous stem cell therapies aimed at precisely replacing neurons after localized injuries.”

Planarians can be found in freshwater, salt water, and even on land. They don’t have circulatory or respiratory systems. But they do have stem cells that can differentiate into whatever their body needs at a given time. Using stem cells, planarians can regrow their entire body from just a sliver of a body fragment. They can rebuild tissues, muscles, and even their brain. Planarian flatworms are known for their regenerative abilities, including de novo brain regrowth after nearly any injury,” the authors wrote. “Critically, neurons are produced in the correct numbers, diversity, pattern, and connectivity to restore function … In addition to regenerative capacity, the planarian nervous system has spatial and cell type complexity, making it suitable for study.”

But how do these tiny creatures know what type of cell to make and where to send it? “… the full pathway from pluripotent stem cell to mature neuron has not been determined for any cell type in the planarian nervous system,” the authors stated. “To better understand how regenerative neurogenesis proceeds in planarians, we focused on a single, conserved cell type: dopaminergic neurons.”

Known as the “feel good” chemical, dopamine is more than just the brain’s reward and pleasure chemical. It also acts as a signal to help neurons communicate with one another and plays a key role in controlling movement. People with Parkinson’s disease, for example, experience tremors and stiffness due to low levels of dopamine.

Through their study the researchers identified almost a dozen genes responsible for instructing stem cells to turn into dopamine-producing neurons and directing those new neurons to the right locations in the worm’s body. “Altogether, we identified ten genes and characterized six genes critical for specifying mature dopaminergic neurons throughout the planarian nervous system, identifying factors that regulate both neurotransmitter identity and cellular location,” they wrote. “Our results demonstrate that planarian neurogenesis requires coordination of factors that initiate neurotransmitter choice and regional location.”

When the researchers knocked out some of the genes discovered in this study, they found the planarians struggled to make new dopamine-producing neurons and also experienced slow movement, similar to the effects of low dopamine in people and other mammals.

Currently, healthcare providers don’t have many options to treat conditions like Parkinson’s, Alzheimer’s or traumatic brain injuries. Harnessing the body’s own cells in the same way planarians do to heal wounds would be a game changer. “The ability to create new neurons in predictable types, numbers, and locations for a given injury or disease would revolutionize treatments of neurodegenerative diseases and other brain injuries,” the researchers noted in their paper. “Our work aims to leverage highly regenerative animals to understand principles of successful neuron replacement.”

Roberts-Galbraith  added, “We figured out the genetic recipe for making these cell types in planarians. We’re hoping this work helps others figure out how to create dopamine-producing neurons from stem cells that can be more effectively transplanted into patients.”

The Roberts-Galbraith lab in the department of cellular biology is part of UGA’s Regenerative Bioscience Center, an interdisciplinary research hub focused on the potential of regenerative medicine.

The post Genes Involved in Flatworm Brain Regeneration Identified appeared first on GEN - Genetic Engineering and Biotechnology News.

Addressing investors at its 2026 Capital Markets Day, Novo CEO Maziar (Mike) Doustdar and other company executives laid out a series of initiatives aimed at restoring its edge in metabolic and other drugs by growing and diversifying its pipeline, as well as driving sustainable growth, and delivering attractive returns.

To that end, Doustdar and colleagues said Novo planned to launch “more than five multi-blockbusters” or drugs with multiple billions of dollars in sales every year through 2030. Those five are expected to emerge from more than five Phase III programs in obesity and diabetes, and another 5+ Phase III programs in other therapeutic areas.

Doustdar also committed Novo to generating more than DKK 150 billion (just over $23 billion) in risk-adjusted pipeline sales by 2035, a figure that includes current pipeline assets. Novo plans to combine internal pipeline growth with external growth through merger-and-acquisition (M&A) activity.

“Novo is targeting 2026-2030 revenue growth in line with industry peers, likely underwhelming for investors,” cautioned Evan David Seigerman, a managing director and head of healthcare research at BMO Capital Markets, in a research note.

Seigerman cited a consensus of analysts that estimates a 3.53% compound annual growth rate (CAGR) for Novo, vs. ~3.65% CAGR for its pharma peers. However, he added, “Novo’s outlined growth expectation appears already priced in to [Wall] Street estimates, reading negatively to shares.”

Key to Novo’s new strategy, Doustdar said, was planning for the eventual loss of U.S. patent exclusivity in 2032 for its best-selling drug semaglutide, the glucagon-like peptide-1 (GLP-1) drug marketed as Ozempic^® for type 2 diabetes in adults and as Wegovy^® for obesity/weight control—what the CEO called “the elephant in the room.”

“We plan to come on the other side of the LOE [loss of exclusivity] as a bigger company than we are today and a much more diversified version of it,” Doustdar said. “We created an incredibly attractive market, and now almost every other single pharma company, big or small, is trying to come and compete with us. We need to be ready for that.”

‘Not seeing concrete news’

Those and other priorities laid out at the annual capital markets event failed to reassure Novo investors. The company’s primary shares on Nasdaq Copenhagen slumped nearly 8% this morning from DKK 281.55 ($43.19) to an even DKK 260.00 ($39.89). On the New York Stock Exchange, Novo’s American depositary receipts (ADRs) also tumbled 8% from $43.24 to $39.81.

“Investors are selling the shares because they are not seeing concrete news that could drive the stock higher,” Per Hansen, investment economist at Nordnet, wrote in a research note, as reported by Bloomberg News.

Speaking on CNBC, Hansen elaborated: “Investors hoped for a project ‘miracle’ that could turn the momentum around short term. For obvious reasons that miracle does not exist.”

Markus Manns, a portfolio manager ​at Union Investment, told Reuters he was less than impressed by Novo’s projections of 2030 sales and a “broadly stable” operating margin.

“They (also) did not say much in terms of ‌how to ⁠tackle the semaglutide patent expiration in 2032,” said Manns, who added that he thought Novo made a credible case for pursuing next-generation obesity drugs and a broader early-stage pipeline.

In its presentation, Novo detailed the drugs it expects to launch each year through 2030—starting with next year, when the company plans to launch once-weekly CagriSema (cagrilintide and semaglutide), a diabetes and obesity drug which combines the long-acting amylin receptor agonist with the GLP-1 receptor agonist. Cagrilintide and a high-dose version of CagriSema are scheduled for a 2028 launch, while 2029 is expected to deliver launches of high-dose cagrilintide; zenagamtide, a multi-receptor peptide agonist targeting GLP-1, amylin, and calcitonin receptors; an oral form of zenagamtide; and a next-generation GLP-1.

In 2030, Novo’s launch calendar includes a monthly-dose or “QM” GLP-1; a thermostable GLP-1; an oral high-yield GLP-1; Amylin 355 and an oral version, both long-acting amylin analogues; an oral ACSL5 inhibitor LX9851, co-developed with Lexicon Pharmaceuticals; and UBT251, a long-acting synthetic peptide triple agonist that targets GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors and is being co-developed by Novo with Chinese-owned United Biotechnology.

Monday’s selloff of Novo shares and ADRs lowered the company’s one-year stock performance to a 33% decline year over year on Nasdaq Copenhagen and a 35% drop on the NYSE.

By contrast, shares of Novo’s archrival in obesity and diabetes drug development, Eli Lilly (NYSE: LLY), have soared 55% year over year, from $754.95 on September 22, 2025 (September 21 was a Sunday) to $1,164.66, up 1% from Friday’s close of $1,152.93.

While Bagsvaerd, Denmark-based Novo Nordisk was first to market with a GLP-1 drug when Ozempic became commercially available in February 2018, Indianapolis-based Lilly has grown to a majority share of GLP-1 drug sales—though Lilly’s blockbuster tirzepatide, marketed for diabetes as Mounjaro^® and for obesity as Zepbound^®, are dual-agonists of GLP-1 and GIP receptors.

2-to-1 sales edge

Lilly has grown its GLP-1-based drug sales so far this year to a nearly 2-to-1 edge over Novo. The two Lilly drugs have racked up a combined $27.6 billion-plus in revenue—$18.605 billion for Mounjaro, $9.088 billion for Zepbound—accounting for about 65% of Lilly’s total $42.773 billion in revenue between January and June 2026.

By contrast, Novo’s GLP-1 blockbusters have racked up a combined DKK 102.393 billion ($15.715 billion) in sales in the first half of 2026, accounting for about 69% of the company’s total DKK 148.551 billion ($22.798 billion) in adjusted sales.

Ozempic garnered DKK 59.2 billion ($9.085 billion), down 8% from DKK 64.52 billion ($9.902 billion) year over year, while its injectable Wegovy generated sales of DKK 37.719 billion ($5.789 billion), up 2% from DKK 36.888 billion ($5.661 billion) in Q1-Q2 2025. The company also made DKK 5.474 billion ($840 million) in sales from oral Wegovy, which reached the U.S. market on January 5.

Lilly’s competing oral obesity drug Foundayo^® (orforglipron), a small molecule GLP-1 receptor agonist, generated $98 million in its first quarter on the market, having won FDA approval on April 1.

Doustdar took Novo’s helm in August 2025, intent on regaining the company’s competitive edge in GLP-1 based obesity and diabetes drugs after Lilly’s sales successes with Mounjaro and Zepbound. A year ago this month, Doustdar led the company’s deepest personnel reduction, which eliminated about 9,000 jobs.

In addition to those initial layoffs, Novo said Monday that 4,000 additional staffers exited the company, resulting in 13,000 fewer employees than a year ago, bringing the company’s workforce down to approximately 66,000 employees.

Novo said its restructuring generated more than DKK 10 billion ($1.534 billion) in savings that is being allocated to its R&D operations, commercial growth brands, and manufacturing right-sizing efforts. The company also said it reduced its spending on external services by ~30% year-to-date and has renegotiated agreements with suppliers to squeeze out further savings.

Flurry of announcements

In the week leading to and including Monday’s Capital Markets Day, Novo issued a flurry of announcements—including a poke at Lilly by highlighting during the event positive topline results from the Phase III REIMAGINE 5 trial (NCT06534411) and REDEFINE 9 trial (NCT06388187) assessing CagriSema, which the company trumpeted as “Novo’s next innovation in weight management and type 2 diabetes.”

In REIMAGINE 5, CagriSema 1.0 mg/1.0 mg showed superiority to tirzepatide 5 mg for weight loss, achieving an estimated average weight loss of 12.4%, compared with 9.1% for the Lilly drug. CagriSema also confirmed a non-inferior reduction in HbA_1c of 1.71% vs. 1.67% for tirzepatide.

In REDEFINE 9, CagriSema 1.0 mg/1.0 mg showed a dramatic weight reduction of 21.0% vs. 2.0% for placebo, meeting that study’s primary superiority endpoint. CagriSema also showed greater improvements than placebo across prespecified endpoints that included systolic blood pressure, waist-to-height ratio, and fasting lipid profile.

The rush of announcements started September 14 with a rebrand that shortened the company’s name in marketing materials to “Novo,” accompanies by an updated Apis bull logo, while keeping “Novo Nordisk” as its legal name.  The company also unveiled a new slogan, “Lasting Health Starts Now.”

“The rebrand is designed to be more memorable and relevant to the way people engage with their health today,” Novo stated in a press release announcing the rebrand. “It also reflects the company’s ambition to bring breakthrough science closer to people’s daily lives and to strengthen recognition and trust as Novo reaches more people in more ways.”

Anthropic, Orbis partnerships

Novo also announced a collaboration of undisclosed value with Anthropic (draft Form S-1 Registration Statement filed June 1) to bolster artificial intelligence (AI)-based drug development. Novo agreed to use Anthropic models and Claude Science to advance scientific reasoning for R&D and agentic software engineering, with the aim of helping Novo discover and develop new treatments faster.

Launched in June, Claude Science is an AI workbench for scientists that consolidates fragmented research tools, including more than 60 scientific databases and connectors pre-configured for genomics, proteomics, structural biology, and more, into a single reasoning layer.

On Thursday, privately held Orbis Medicines announced an up-to-$1.4 billion strategic collaboration and license agreement with Novo, bringing together the two Danish-based drug developers to discover and develop an undisclosed number of next-generation oral macrocycle therapeutics for unspecified cardiometabolic diseases.

The potential $1.4 billion reflects an upfront payment and payments tied to achieving development and commercial milestone payments. Copenhagen-based Orbis will also gain a strategic investment of undisclosed amount from Novo, and potentially gain tiered royalties on future product sales.

Novo plans to apply Orbis’ lab-in-the-loop ⁿGen platform which integrates generative AI and high-throughput synthesis, using a multi-parameter optimization (MPO) engine to design ⁿCycles with desirable properties—detailed in a 2023 Nature Chemical Biology paper as including target biding and other key properties for oral availability, such as proteolytic stability, membrane permeability and metabolic stability. Orbis says it continuously improves its ⁿCycles through one of the industry’s largest experimental macrocycle datasets, which the company generates in real time via its platform.

Novo’s interest in macrocycles appears to reflect a desire to overcome limitations associated with traditional oral peptide treatments, such as low digestive absorption. The 2023 paper showed Orbis’ macrocycles to have an oral bioavailability of up to 18% in rats: “This method for generating orally available peptides is general and provides a promising push toward unlocking the full potential of peptides as therapeutics.”

Other announcements:

• Frehemgo^® (denecmig) won a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use recommending approval for the next-generation factor VIIIa mimetic bispecific antibody to treat hemophilia A, with or without inhibitors, in adults and children.
• Denecimig generated positive results in the Phase III FRONTIER5 trial (NCT05878938), showing that a direct switch to a subcutaneous denecimig pen injector from a vial and syringe injection system for a current Hemophilia A treatment emicizumab, marketed by Genentech as Hemlibra^®, was well tolerated with no unforeseen safety concerns in adolescents and adults with hemophilia A.
• Sogroya^® (somapacitan) also won a positive CHMP opinion for the human growth hormone analogue as a once-weekly treatment for children with idiopathic short stature (ISS) with persistent growth disturbance. The drug won FDA approval in 2020.

Leaders & Laggards

• BlossomHill Therapeutics (Nasdaq: BLSM) shares jumped 21% over two days, from $22.17 Tuesday to $26.82 Thursday, after the small molecule cancer drug developer announced positive updated data from the ongoing Phase I/II SOLARA trial (NCT06706076) assessing BH-30643 in non-small cell lung cancer (NSCLC) patients with secondary epidermal growth factor receptor (EGFR) resistance mutations such as EGFR C797S. In patients with EGFR C797S-positive resistance to prior EGFR inhibitor treatment, with or without concurrent T790M, BH-30643 showed a 45% objective response rate (18 of 40 patients) and an 88% disease control rate (35 of 40 patients). At the time of efficacy follow-up, 25 of 40 patients (63%) remained on treatment with a median follow-up of 6.9 months. BlossomHill presented the data at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer in Seoul.
• Xenon Pharmaceuticals (Nasdaq: XENE) shares tumbled 31% from $57.35 to $39.75 Friday, after the neuroscience-focused drug developer acknowledged that it voluntarily paused enrollment of new patients in two Phase III programs encompassing five trials assessing its potent KV7 potassium channel opener azetukalner—the three-program X-NOVA program in major depressive disorder (MDD), and the two-trial X-CEED program in bipolar depression—following an analysis of neuropsychiatric adverse events. “In a very small number of patients, we have seen an adverse event captured under the broad preferred term of psychosis,” Xenon chief medical officer Christopher Kenney, MD, told analysts on a conference call. Those events had not previously been seen in the Phase II X‑NOVA trial in MDD (NCT05376150), Xenon said, adding that the observed events, their rate of occurrence, and their severity, were consistent with the known safety and tolerability profile of azetukalner and its mechanism.

The post StockWatch: Novo’s 2030 Strategy Underwhelms Investors at Capital Markets Day appeared first on GEN - Genetic Engineering and Biotechnology News.

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Alex Fuchs

Director of Product Innovation
Single Use Support
Colder Products Company

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Panelist

Alex Fuchs

Alexander Fuchs is the director of product innovation at Single Use Support. Due to his highly technical education and intensive insights, he has a wide range of experience and knowledge in various industries, such as jewelry, manufacturing, and biopharma, as well as multiple areas of activity. Passionate about automation, engineering, and process management, Alexander contributes to the innovative focus of advancing fluid and cold chain management within the biopharmaceutical industry.

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Jascha Rosenbaum

Regional Director for Applications & Business Development
Colder Products Company

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Panelist

Jascha Rosenbaum

Jascha Rosenbaum is the regional director for applications and business development in Europe. Jascha holds a master’s degree in chemical engineering, and he has worked in the single-use industry for the last 10 years in both the U.S. and Europe. He has supported some of the largest biopharmaceutical manufacturers across Europe, where he has experience at every stage of single-use solutions.

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In cell and gene therapy manufacturing, fluid transfer and freeze-thaw workflows are paramount to process efficiency, product quality, and operational flexibility. From scaling and closed-system processing to automation and the growing use of cryopreservation, manufacturers are rethinking how materials move through the process—both during manufacturing and between unit operations.

In this GEN webinar, our expert speakers will discuss the latest trends, challenges, and innovations shaping fluid transfer and freeze-thaw workflows. The panel will explore how cell and gene therapy manufacturers are addressing complex process requirements while reducing manual interventions, minimizing contamination risk, improving workflow efficiency, and preparing processes for scale. Key takeaways from the webinar include:

• Emerging approaches to fluid transfers,
• Single-use technologies and sterile connections,
• Freeze-thaw considerations,
• Automation and closed processing,
• Strategies for building more flexible and robust workflows for cell and gene therapy manufacturing

A live Q&A session will follow the conversation offering you a chance to pose questions to our expert panelists.

Produced with support from:

The post Emerging Trends in Fluid Transfers and Freeze-Thaw Workflows appeared first on GEN - Genetic Engineering and Biotechnology News.

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Joshua Michael Hare, MD

Founding Director,
Interdisciplinary Stem Cell Institute
University of Miami
Miller School of Medicine

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Panelist

Joshua Michael Hare, MD

Joshua Hare, MD, is a board-certified practicing cardiologist and holds the Louis Lemberg Professorship of Medicine at the University of Miami Miller School of Medicine. Hare currently serves as the founding director of the Interdisciplinary Stem Cell Institute at the University of Miami. He is widely published and has authored or co-authored over 450 articles. Hare has pioneered the use of cells as medicines for human heart disease, Alzheimer’s disease, stroke, and diseases of aging. His research has been funded by the National Institutes of Health and the Department of Defense, and he currently oversees multiple clinical trials using cell and gene therapy to treat human ischemic and non-ischemic cardiomyopathy.  Hare is an inducted member of the American Association of Physicians and the National Academy of Inventors.

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Cardiovascular diseases offer a compelling opportunity for regenerative and cellular therapies that can repair damaged tissue, promote vascularization, modulate inflammation, or restore cardiac function. However, translating research advances into meaningful therapeutics requires connecting a strong biological rationale with appropriate cell types, indications and therapeutic strategies, and patients who are most likely to benefit.

In this GEN webinar, our expert speaker will examine how therapeutically relevant research is helping shape the development of cell therapies for cardiovascular disease. His presentation will cover strategies for selecting indications, biological targets, and cell types based on disease pathophysiology and unmet clinical need. Attendees will also learn about the path from laboratory research to clinical investigation, including considerations around cell delivery and patient selection, and the clinical endpoints needed to evaluate safety and therapeutic benefit.

A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelist.

Produced with support from:

The post Advancing Cell Therapy for Cardiovascular Disease appeared first on GEN - Genetic Engineering and Biotechnology News.

Sanfilippo syndrome type A (MPS IIIA) is a rare, fatal lysosomal storage disease that primarily affects the central nervous system (CNS) and is marked by rapid neurodegeneration beginning in early childhood. MPS IIIA is estimated to affect 3,000 to 5,000 patients worldwide, with a median life expectancy of 15 years.

‍Fayuvi is the first FDA-approved gene therapy manufactured using the Andelyn AAV Curator^® Platform process. ‍

“We congratulate Ultragenyx on this significant achievement and recognize the MPS IIIA community, investigators, and everyone who contributed to advancing this program,” said Wade Macedone, CEO of Andelyn Biosciences. “We are proud to manufacture an FDA-approved gene therapy for commercial use using an AAV Curator Platform process.”

Andelyn’s AAV Curator Platform uses a configurable, data-informed approach to AAV process development and manufacturing, according to Macedone, who added that it integrates process knowledge, modular manufacturing strategies, and fit-for-purpose analytics to support gene therapy programs from development through commercial launch.

The post Andelyn Curator Biomanufacturing Platform Supports Fayuvi Gene Therapy Approval appeared first on GEN - Genetic Engineering and Biotechnology News.

The Mayo Clinic last week launched Precure with founding partner Thermo Fisher Scientific to help transform how the life sciences community understands the biological changes that occur as disease develops before symptoms occur. Precure brings together clinical expertise, de-identified longitudinal health information, and population-scale molecular data to accelerate the development of new approaches with healthcare applications.

Helix will provide both advanced AI tools for delivery of genomics into the clinic and biomarker driven research, and population scale multiomic capability that encompasses clinical whole genome sequencing (WGS) and research grade proteome sequencing. Linked with longitudinal clinical information and high performance compute infrastructure, the objective is to create new opportunities for prevention, diagnosis, and treatment, according to Aaron Mangold, MD, chief medical officer, Precure.

“Our goal is to generate genomic information that can help inform patient care while creating a powerful resource for discovery,” said Mangold. “We are working to make clinical whole genome sequencing and multiomics a foundation of care, helping us detect disease sooner and act earlier.”

Building on Mayo Clinic’s Tapestry study, which utilized Helix’s Exome+ sequencing technology and reached 100,000 participants, Precure is extending that collaboration by leveraging Helix’s experience providing workflow orchestration, (CLIA/CAP) genomic sequencing, data infrastructure, and AI tools to its health system partners.

Precure and Helix have selected Ultima Genomics’ UG200 Ultra Sequencing Platform as part of the program’s large-scale multiomics initiative. Helix will use a fleet of Ultima’s next-generation platforms to generate genomic data for WGS and read-out for proteomics at scale.

“The genome is becoming an enduring patient resource, providing a precision baseline for a lifetime of care,” noted James Lu, MD, PhD, CEO of Helix. “Helix brings together the laboratory and data capabilities to make this possible at scale.”

Helix joins Precure as a collaborator and minority owner. Mayo Clinic’s involvement in Precure is intended to advance its nonprofit mission. Any financial returns to Mayo Clinic would be reinvested in its mission of patient care, research and education. Visit mayo.edu/research/precure for more information.

The post Precure Selects Helix as Multiomics Lab and AI Tools Provider appeared first on GEN - Genetic Engineering and Biotechnology News.

Some strains are watched more closely than others, and the highly pathogenic avian H5N1, a subtype of the influenza A virus that causes avian influenza (“bird flu”), may garner the most attention as it is regarded as one of the largest pandemic threats.

Although H5N1 primarily infects birds, it can also infect mammals. Human infections are uncommon and have generally occurred after close contact with infected animals or contaminated environments. The World Health Organization reports no sustained person-to-person transmission.

The Global Virus Network (GVN) is closely monitoring detections of H5N1 in several mammal species in Australia as the virus continues to spread. Last week, Australian authorities confirmed the first detection in an Australian sea lion, an endangered species, at Seal Bay on Kangaroo Island.

Australia reported its first confirmed detection in a mammal on August 23, when a long-nosed fur seal found at Beachport in South Australia tested positive. A second long-nosed fur seal near Kangaroo Island was confirmed two days later and subsequent detections included red foxes and a common dolphin. Australian authorities report no evidence of mammal-to-mammal transmission of the virus in Australia.

The detections show the virus infecting several mammal species in Australia within weeks of its first reported appearance in the country’s wildlife. Globally, H5N1 has infected a growing range of mammals, including seals and other marine mammals, dairy cattle, cats and wild carnivores. Scientists are monitoring these infections for changes in the virus and evidence of transmission between mammals.

“Given what we have seen with this H5N1 genotype in seal and sea lion populations overseas, a spillover into Australian marine mammals was a possibility we had been concerned about and actively monitoring for,” said Michelle Wille, PhD, an avian influenza researcher affiliated with the University of Melbourne and the WHO Collaborating Centre for Reference and Research on Influenza and the Peter Doherty Institute for Infection and Immunity, a GVN Center of Excellence in Australia. “While it is sobering to see that possibility become a reality, the priority now is detailed genomic analysis of this and any future detections. We need to closely monitor for mutations associated with better adaptation to mammals and determine whether infections represent separate spillover events from birds or evidence of transmission between seals. That distinction will be critical to understanding the risk posed by the virus as it continues to circulate in wildlife.”

Australia first detected H5N1 clade 2.3.4.4b in wild seabirds in June. The virus has since been found in wild birds across several parts of the country. As of September 17, Australia had reported 576 confirmed events in wildlife, including mass mortality events in greater crested terns. An event may involve one or more animals.

In April 2025, GVN published an analysis in The Lancet Regional Health—Americas calling for stronger surveillance, biosecurity, genomic monitoring and preparedness as H5N1 spread. In April 2026, GVN issued a statement on H5N1 vaccine developments, emphasizing the need for continued vaccine development and broader pandemic preparedness.

“Australia is another reminder that H5N1 is a global animal health issue with implications for human health that we need to continue watching closely,” said Sten H. Vermund, MD, PhD, GVN’s chief medical officer and dean of the University of South Florida College of Public Health. “There is no reason for alarm, but there is every reason to remain vigilant. Surveillance across species, rapid genomic analysis and open sharing of what we learn give us the best chance to recognize an important change in the virus early.”

The post H5N1 Spreads Among Australian Wildlife as Flu Season Ramps Up appeared first on GEN - Genetic Engineering and Biotechnology News.

Brenipatide is a dual-agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors—the same modality as its blockbuster tirzepatide, marketed for type 2 diabetes in adults as Mounjaro® and for obesity as Zepbound®. The two drugs have racked up a combined $27.6 billion-plus in revenue for Lilly so far this year—$18.605 billion for Mounjaro, $9.088 billion for Zepbound—accounting for about 65% of Lilly’s total $42.773 billion in revenue between January and June 2026.

Unlike tirzepatide, brenipatide is designed to target GIP and GLP-1 receptors in central nervous system and inflammatory pathways that include receptors linked to reward and addiction in the brain.

At the Psych Congress 2026, held in New Orleans, Lilly presented “Brenipatide, a GIP/GLP-1 Receptor Agonist: Clinical Data Supporting Dose Selection for Substance Use, Psychiatric and Immunologic Disorders,” a poster detailing results from its Phase I J2S-MC-GZMD trial (NCT06606106).

The Lilly-sponsored study was designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of brenipatide in healthy, overweight, and obese participants as measured by body mass index (BMI), with the goal of determining a brenipatide dosing regimen suitable for substance use, psychiatric, and immunologic disorders.

Brenipatide showed a mean half-life ranging between 9.08 days and 12.5 days, with the longer half-life seen in participants given the highest dose of the drug at 4.5 mg. Participants treated with brenipatide received doses of 4.5 mg or lower (0.3 mg, 0.75 mg, 1.5 mg, or 3 mg).

“That allows us to have a durability of exposure that can go beyond the weekly dosing interval, which is what we’re testing benepatide in within the neuroscience space,” Robert Nicholson, PhD, associate vice president, U.S. & global neuroscience medical affairs, psychiatry & substance use disorders with Eli Lilly, told GEN.

The data, Lilly researchers concluded in the poster, “support the selection of weekly maintenance doses across a broad range of BMIs, including normal body weight, that optimize safety, tolerability, and incretin pharmacology” in substance use, psychiatric, and immunological disorders.

“Potentially a really good option”

“As we think through those living with substance use disorders, psychiatric disorders, and certainly in our Phase III trials right now within alcohol use disorder and those with recurrent major depressive disorder, that weekly dosing could be potentially a really good option for those people,” Nicholson added. “Having that longer half-life is some of the reason why we think there’s a distinct profile for brenipatide relative to currently available incretin therapies.”

The Phase I trial was an investigator- and participant-blind, multiple ascending dose study of brenipatide with an eight-week follow-up period. More than 200 people participated in the trial, a population split into three parts:

• Part A: BMIs of 27.0–45.0 kg/m2, randomized 16:2 (96 to brenipatide, 12 to placebo).
• Part B: BMIs of 22.0–26.9 kg/m2: randomized 16:2 (64 to brenipatide, 8 to placebo).
• Part C: BMIs of 22.0–26.9 kg/m2 in Japanese and Chinese participants, randomized 6:2 (24 to brenipatide, 8 to placebo).

Part A participants at the highest 4.5 mg dose showed a mean plasma concentration of the drug of just over 1,000 ng/mL on Day 78, with plasma concentration being dose-dependent—a correlation that was also seen with participants in parts B and C, Lilly said.

The Phase I trial also showed brenipatide to have met the study’s primary outcome measure of positive safety data measured by one or more adverse events, including severe and treatment-emergent, that investigators considered related to the study drug. Researchers reported no deaths or serious adverse events (SAEs), with only four participants (2.2%) discontinuing the study due to a treatment-emergent adverse event (TEAE). Brenipatide was generally well-tolerated across all doses studied in participants with a wide range of BMI and different ethnicities, Lilly said.

The most frequently reported TEAEs were gastrointestinal (GI)-related, with an overall GI TEAE frequency of 25% in both brenipatide- and placebo-treated participants. Dysesthesia-related TEAEs were reported in 15.2% of brenipatide-treated participants, but none on placebo.

The GI tolerability could be related to brenipatide’s low peak-to-trough ratio, which Nicholson said is more narrow than for the other incretin therapies that are currently available.

MDD, AUD trial designs

Lilly is building on that early success in part by carrying out a pair of Phase III trials for brenipatide in two indications with large patient populations. During Psych Congress 2026, Lilly presented posters detailing the designs of those two trials—one assessing brenipatide in MDD, the other in alcohol use disorder AUD.

In MDD, Lilly has launched the Phase III RENEW-MDD-1 trial (NCT07412756), a multicenter, double-blind, placebo-controlled study evaluating brenipatide plus standard of care (SoC) compared to placebo plus SoC in delaying the return of major depressive symptoms.

The trial is designed to enroll approximately 1,000 participants across 14 countries. The primary endpoint is time to relapse, measured in days from randomization, while the study has numerous secondary endpoints that include MADRS Total Score, PGI-S, GAD-7 Total Score, ReQoL-20 Total Score, patient-rated symptom and disease severity, PROMIS Short Form, SDS global functional impairment score, and body weight (on and not on an atypical antipsychotic).

In AUD, Lilly has launched a pair of 56-week Phase III trials: RENEW-ALC-1, designed to assess brenipatide in participants with moderate-to-severe AUD (NCT07219966); and RENEW-ALC-2 (NCT07219953), intended to evaluate the safety and effectiveness of brenipatide compared to placebo in people with AUD and hazardous alcohol use. The two trials are designed to enroll 2,200 participants—1,100 each—in eight countries.

Primary outcome for both studies is change in drinking patterns using the Timeline Followback Method (TFBM).

Straight to Phase III

For both MDD and AUD, Lilly advanced brenipatide straight to Phase III, launching the late-stage trials directly following positive Phase I studies, rather than pursuing Phase II studies first, because of the patient populations for both conditions.

In MDD, an estimated 21 million American adults (about 8.3% of the adult population) had experienced a major depressive episode each year as of 2021, according to data last updated in 2023 by the NIH’s National Institute of Mental Health. Globally, approximately 322 million people have MDD, according to a 2023 study cited by the World Health Organization.

As for AUD, 27.9 million Americans ages 12 and older had an alcohol use disorder in the past year, according to data from the National Survey on Drug Use and Health published in 2025 by the NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA). An estimated 400 million people, or 7% of the world’s population aged 15 years and older, lived with alcohol use disorders, according to WHO data last updated in 2024.

“When we look at AUD and MDD, both of those have existing needs that when people think about either having different or better therapies, as well as different types of outcomes, those are the needs where we think about the opportunity and why we thought it was worth going straight to Phase III in those conditions,” Nicholson explained.

FDA-approved AUD drugs

According to NIAAA, three drugs are FDA-approved for AUD: Naltrexone, designed to help reduce the urge to drink, available in several branded or generic versions; acamprosate, a pill sold in several generic versions that is designed to decrease the negative symptoms that are sometimes felt during abstinence from alcohol, making abstinence easier to maintain; and disulfiram, a pill that discourages drinking by causing unpleasant symptoms when alcohol is consumed, and is also sold in generic versions.

“The current medications themselves that are approved for alcohol use disorder assume abstinence is what you’re either supporting further or driving towards. But for some individuals, that may not be the outcome that they’re thinking about. So from an AUD perspective, having a different or potentially better treatment or treatment or an outcome that we’re aiming for could be important,” Nicholson said.

That explains, he said, why Lilly’s focus in the AUD trials is an overall change in drinking patterns: “It’s something that is a little different from thinking about abstinence being what we’re aiming for, specifically.”

The Phase III trials in AUD and MDD are among 13 Phase II and III studies in progress for brenipatide, Nicholson said. Other potential indications for the drug that are under study include Phase II studies currently going on for two substance abuse indications, tobacco use disorder and opioid use disorder; and two psychiatric indications, bipolar disorder and schizophrenia.

In the immunology space, brenipatide is being evaluated in forms of asthma, irritable bowel syndrome, and chronic obstructive pulmonary disease (COPD).

The post Lilly’s GIP/GLP-1 Candidate Brenipatide Shows Early Clinical Promise in Substance, Psych Disorders appeared first on GEN - Genetic Engineering and Biotechnology News.

And now the venture studio, which was formerly called Negev Labs, has made its first move towards those goals by spinning out its first portfolio company, Ariadne Bio, with a lead program already in hand. Raz steps into the role of CEO for the company and Daniel Jeffries, PhD, a partner at Palomar Labs, will take on the role of chief development officer for the company. Ariadne Bio will focus on developing AB-300, a clinical-stage molecule that functions as a non-hallucinogenic serotonin 2A receptor agonist. The company is developing the molecule to treat apathy in people with Parkinson’s disease.

“A significant portion of people with Parkinson’s will lose the drive to do the things that make life worth living, and not a single approved medicine is designed to bring it back,” Raz said. “We built Ariadne Bio around a single question: whether motivation can be restored pharmacologically. AB-300 is how we intend to answer it.” 

Ariadne Bio makes a compelling case for targeting apathy. As Jeffries notes, “apathy is among the most disabling non-motor features of Parkinson’s disease.” The condition is defined clinically as a persistent reduction in goal-directed behavior. It is estimated to affect approximately 40% of people with Parkinson’s disease over the course of the illness. 

Higher rates of the condition are reported in people in the mid to late stages of the disease. In fact, studies of caregiver burden in Parkinson’s rank neuropsychiatric symptoms like apathy ahead of motor symptoms as drivers of distress. It is important to note here that while apathy and depression have some overlapping features, they are distinct conditions. Selective serotonin reuptake inhibitors (SSRIs) remain the appropriate treatment for Parkinson’s associated depression, but some evidence links their use to emotional blunting and worsening apathy. 

In contrast, there are currently no approved therapies for apathy in any indication. If AB-300 successfully makes its way through clinical trials and clears regulatory approval, it could be one of the first. And Raz and his team are driven to accomplish that goal. In fact, this is the second neuropsychiatry-focused company that Raz is launching. Previously, he founded Eleusis, which claims to be the first company that was dedicated to developing medicines derived from psychedelic compounds. Eleusis was acquired by Beckley Psytech in 2022. That company combined Atai Life Sciences to form AtaiBeckley in 2025. As of July, 2026, Eli Lilly entered into a definitive agreement to acquire AtaiBeckley. 

A non-hallucinogenic history

Raz moved to Palomar Labs after a stint at Beckley Psytech because of what he saw as a “significant opportunity” with similar themes to psychedelics—drugs with demonstrated therapeutic potential that never translated into U.S. Food and Drug Administration-approved therapies. There are several drugs that could fall into this category but Raz admits he is a bit biased towards serotonin therapies because of his background in psychedelics. “Coming out of the psychedelic space, the way I view it is that the first generation of that drug class were these very potent classical psychedelics like psilocybin and LSD,” he said during the conversation. The second generation featured drugs with formulation changes that altered their pharmacodynamics in different ways. 

Raz and his team are most interested in what he categorized as the third-generation. These are potential therapies that activate the same receptors as psychedelic drugs without the corresponding hallucinogenic effects, making them ideal for use in older adults. AB-300 is one such compound. For some of its back story, the compound is based on one that was previously tested in the 1970s and documented to lack hallucinogenic effects, Jefferies told GEN. Since then, several groups have dug into why this particular molecule does not cause hallucinations like other serotonin agonists. 

Earlier this year, scientists published a paper in January in Nature that pointed to signaling bias as the likely reason. “When you activate serotonin 2A, there’s multiple intracellular pathways that can be engaged,” Jeffries said. According to the paper’s findings in a preclinical model, the parent compound that AB-300 is based on “preferentially activated the non-hallucinogenic pathway” without removing any therapeutic benefit.

The fact that this compound does not act on dopamine receptors is crucial. “Classically, mental stimulation comes through a variety of drugs that either block the re-uptake of dopamine or activate dopamine receptors directly,” Raz notes. “The problem of course is that they aren’t necessarily well tolerated by older adults. And so we saw the promise of developing a therapy that indirectly modulates motivation through serotonin receptor activation” without the hallucinogenic effects. Apathy in Parkinson’s disease cases is the immediate target but Raz acknowledged that there are other diseases of aging that involve unaddressed apathy. And Ariadne Bio is actively exploring ways to address those conditions in future. “The more research we did, the more we realized how profound the unmet need there was.”

Building up to Phase Ib

In May 2026, at the American Society of Clinical Psychopharmacology, (ASCP) Ariadne Bio presented results from tests of its lead candidate in a preclinical model of tetrabenazine (TBZ)-induced motivational deficit, assessed by progressive-ratio lever pressing. In this model of effort-based motivated behavior, AB-300 plus TBZ increased motivational behavior by 89% relative to the TBZ only group, which is a statistically significant improvement.  

The company claims that AB-300 is the first serotonin 2A receptor agonist drug candidate shown to restore motivated behavior in a dopamine-depleted model. They also claim that in off-target screening, AB-300 shows no measurable activity at dopamine receptors or the dopamine transporter, which indicates that it engages motivational circuitry through a mechanism independent of dopaminergic signaling. 

Raz and Jeffries dug into the details of the study using the tetrabenazine-induced model in more detail during their conversation with GEN. “One of the interesting things about developing apathy, is that this indication has an in vivo model that’s arguably more translatable than some of the other more mainstream neuropsychiatric indications,” Jeffries explained. Tetrabenazine is an FDA-approved drug used in Huntington’s disease with detailed data on its ability to induce a low motivational apathetic phenotype in clinical and preclinical models. Part of what makes the drug so interesting is that it depletes the levels of circulating dopamine in the brain, similar to what is seen in Parkinson’s cases. 

That is an important point, Jefferies emphasized. Because “essentially what that allows developers to do is to test their investigative agent in a motivational model with the background of dopamine depletion,” he said. In terms of the results, the team saw positive effects at doses that are predicted to be within a therapeutic range in the clinic. Furthermore,  the team also observed some of the negative effects of using SSRIs to treat apathy in their model. These results mirrored clinical observations of patients, whose apathy was treated with SSRIs and saw their symptoms worsen. These results show the efficacy of AB-300 and “it’s giving us a lot of motivation … to move forward,” he added. 

That next step is a Phase Ib clinical trial that will test AB-300 in healthy volunteers and Parkinson’s patients, most of whom will be receiving the current standard of care treatments and potentially on antidepressants for their apathy. In addition to assessing safety and efficacy of the treatment, Ariadne’s team and their partners will also assess potential interactions between their compound and those other drugs. 

The trial will begin likely at the end of Q3 or the beginning of Q4 at centers in Austria and Israel. Ariadne Bio has already had a Type B pre-IND meeting with the FDA regarding the development of AB-300 for Parkinson’s disease-associated apathy. 

The planned trial will be a three-part study, Jeffries told GEN. The first part will be a single ascending dose in healthy patients followed by a single ascending dose in Parkinson’s disease patients. In both parts, the scientist will explore “a variety of biomarkers [and a] range of doses” to identify the maximally efficacious dose. “We have the preclinical data [that] tells us generally where we should be looking, but we need to really see that in patients who are on Parkinson’s disease medications to confirm that in fact that is the right range for what we anticipate to be a clinically effective dose or at least to evaluate that potential,” Raz added. The third part of the trial will be a 28-day placebo-controlled double-blind of AB-300 against placebo in patients with clinically relevant apathy. 

Ariadne Bio’s launch is backed by funding from Palomar Labs as well as from The Michael J. Fox Foundation through its Parkinson’s disease therapeutics pipeline program. That program supports preclinical and translation research aimed at evaluating promising therapeutic approaches and helping to support their clinical development. While Ariadne officials declined to disclose exactly how much it has received in funding, Raz told GEN that the company has enough in house to complete the proposed clinical trial at this time.

The post Palomar Labs Spins Out Ariadne Bio to Advance Non-Hallucinogenic Therapy for Parkinson’s Apathy appeared first on GEN - Genetic Engineering and Biotechnology News.

The discovery overturns a prevailing model of brain development, based on the theory that there is a single progenitor cell early in development that gives rise to the entire brain. This model suggested that all parts of the brain shared a common developmental origin. The newly reported findings show that the human brain consists of two ancient nervous systems cleverly packaged together—a more primitive part that regulates the heart beating, our breathing and other functions, and another part that makes us distinctly human, capable of poetry, mathematics and wondering about our own origins.

The results could help explain why scientists have struggled for decades to grow certain types of brain cells in the laboratory—and it opens new avenues for studying devastating diseases that affect the brain stem, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS).

“We’ve shown for the first time that the front of the brain arises from a totally different progenitor cell than the back of the brain,” said Kyle Loh, PhD, associate professor of developmental biology. “Our discovery means that we can now grow neurons from the back of the brain, the hindbrain, in a petri dish and study their functions.” Loh is senior author, and Carolyn Dundes, PhD, and Rayyan Jokhai are co-first authors of the scientists’ published paper in Nature Neuroscience, titled “Two parallel neural ectoderm progenitors contribute to the developing brain,” in which they concluded that “… the emerging notion of two parallel brain progenitors has a number of ramifications for development, differentiation and evolution.”

The adult brain has three main regions: the forebrain, midbrain and hindbrain. The forebrain handles higher-level thinking—language, consciousness and abstract reasoning. In contrast, the hindbrain, located at the back of the skull and often called the brain stem, controls essential, automatic functions that keep us alive: breathing, sleeping, and regulating our heartbeat and hunger urges. “Consequently, hindbrain injury and diffuse intrinsic pontine glioma (a childhood hindbrain cancer) are both deadly, as they impair consciousness, sensation, reflexes and breathing,” the authors wrote. The hindbrain neurons also control the muscles of the face, tongue and throat, which affect speech and swallowing.

Despite the critical importance of the hindbrain, scientists have struggled for decades to generate human hindbrain neurons in the laboratory. This gap has hampered research into devastating diseases affecting the brain stem, including spinal muscular atrophy and amyotrophic lateral sclerosis.

SMA is a leading genetic cause of death in children under one year of age. ALS, which is often diagnosed between the ages of 40 years and 70 years of age, affects both the forebrain and the hindbrain. In both disorders, certain hindbrain neurons gradually cease to function, and the patient loses the ability to swallow, which can cause pneumonia when food or liquid is inhaled into the lungs; eventually, patients lose the ability to breathe. “… degeneration of hindbrain motor neurons probably compromises eating and swallowing in diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis, leading to choking, aspiration, pneumonia and, in some cases, death,” the team continued.

The researchers’ newly reported discoveries emerged from studying the earliest moments of embryonic development, during a stage called gastrulation when the body first takes shape. Jokhai and Dundes discovered that the hindbrain follows a separate developmental path, running in parallel to, rather than branching off from, the pathway that creates the forebrain and midbrain.

The researchers learned this from examining developing mouse embryos. They identified two different brain progenitor cells. “Two parallel brain progenitors emerge simultaneously during gastrulation: anterior neural ectoderm (forebrain/midbrain progenitor) and posterior neural ectoderm (hindbrain progenitor),” they stated. One, which expresses a gene called Otx2, is destined to become the forebrain and midbrain. The other, which expresses a gene called Gbx2, is committed to forming the hindbrain. They showed that these two cell populations never overlap; they are mutually exclusive from the earliest stages of development. “Differentiation of human pluripotent stem cells into anterior or posterior neural ectoderm-like cells revealed these were lineage committed to forebrain/midbrain versus hindbrain fates, respectively.”

The team then examined the DNA packaging, or chromatin, in these cells. Chromatin is a way cells determine which genes can be easily accessed and which are bundled away out of reach. What they found was striking: The anterior neural ectoderm (aNE; future forebrain and midbrain) and posterior neural ectoderm (pNE; future hindbrain) have fundamentally different chromatin configurations. “They harbored diverging chromatin landscapes foreshadowing future forebrain/midbrain versus hindbrain identities,” the team noted. These differences essentially locked each progenitor cell into its respective fate, like travelers on parallel tracks that never cross.

This revelation explained decades of frustration in the field—scientists had been trying to turn one type of progenitor cell into another that it is fundamentally incapable of becoming. “Previous attempts to make hindbrain neurons likely tried to coax forebrain and midbrain progenitors into hindbrain cells, which our study shows is not possible,” Jokhai said. “In stem cell biology, people are always fixated with creating the end cell type, like the neuron. But it’s important to begin at the earliest stages of embryonic development. Our careful attention to that early time point allowed us to find this fundamental split in brain development.”

Armed with this knowledge, the researchers for the first time successfully coaxed human pluripotent stem cells (a kind of cell that can create any cell in the human body) to become functional hindbrain motor neurons in the laboratory.

These lab-grown neurons displayed all the hallmarks of authentic hindbrain cells: They exhibited waves of electrical activity called action potentials and made proteins that identify the segments of the hindbrain that control facial and swallowing muscles. “Discovering this lineage bifurcation provided a roadmap to differentiate hPS cells into pNE and subsequently specific types of hindbrain neuron in vitro, thus enabling future explorations of human hindbrain biology and disease,” the scientists noted.

Finally, the researchers looked back over 550 million years of evolutionary time. They found the same two-origin brain pattern in chickens, zebrafish and, remarkably, in acorn worms, tiny creatures living on the ocean floor that share a distant common ancestor with humans. “Separate anterior and posterior ectoderm populations arise during gastrulation across deuterostome species as diverse as acorn worm, zebrafish, chicken, mouse and primate, implying that this distinction between two different types of ectoderm predates the origins of chordates and arose ~550–600 million years ago,” the team further stated. Jellyfish, which diverged from humans about 600 to 700 million years ago, have two nervous systems at different ends of their body.

“Our research suggests that evolution took two existing neural systems and pushed them together spatially,” Loh said. “Having the brain as one organ would probably be more efficient, but we rely on this primordial way to make the brain as two separate pieces.”

“I was surprised at our findings because the word ‘brain’ implies a contiguous organ that likely has a singular origin,” Jokhai added. “But even 500 million years ago, there were these separate neural systems, which now almost operate as one, which is very cool.”

The research also has implications for investigating treatments for SMA, ALS and other conditions affecting the brain stem. Until now, studying these diseases has been nearly impossible because scientists cannot obtain brain stem tissue from living patients. The ability to grow these neurons in a dish opens new possibilities for understanding what goes wrong. There’s even an unexpected connection to obesity treatment: The hindbrain contains circuits that regulate hunger—which is precisely how weight-loss drugs like semaglutide work.

The researchers would like to extend their studies to determine the developmental origins of the spinal cord and to learn exactly how SMA and ALS compromise the function of hindbrain neurons. “Now we have a model to better understand these devastating diseases, and work toward regenerative therapies for them,” Jokhai said. “This is a very exciting new frontier in brain research.”

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This month—appropriately Sickle Cell Awareness month—sees the publication of a new popular science book on SCD, Curved Air, written by Kevin Davies, PhD, and published by Harvard University Press. I sat down with Kevin to ask him about the genesis of the book and the extraordinary story of SCD.

(This interview has been lightly edited for length and clarity.)

GEN: Kevin, how did the idea for Curved Air come about?

Kevin Davies: My last book, Editing Humanity, which was about the CRISPR revolution, came out six years ago. Whenever I was asked about the most exciting application of gene editing, I would invariably answer: ‘sickle cell.’ That’s because, like many people, I’d been moved to learn about the journey of Victoria Gray, the first SCD patient to undergo CRISPR cell therapy, back in July 2019. She talked openly about her therapy and recovery in a series of interviews on National Public Radio.

I found it ironic that CRISPR—this incredible 21^st century, Nobel Prize-winning technology for performing DNA surgery—should find its first clinical success treating patients with a disease that, many would argue, has been underfunded and forgotten by large sections of the medical and pharma communities.

I also have to give a shout-out to John Evans, the CEO of Beam Therapeutics. During an interview he gave to GEN about five years ago, John described SCD as ‘the most famous genetic mutation in the world.’ That quote really hit home and gave me added impetus to write the book proposal that became Curved Air.

GEN: I do like the title of the book. Where did it come from?

Davies: As you probably know John, ‘Curved Air’ was a British progressive rock band in the 1970s. I’m a huge fan of the genre, although not that band specifically. But the phrase seemed to fit perfectly. ‘Curved’ reflects the trademark crescent- or sickle-shaped red blood cells (RBCs) in SCD. And ‘Air’ corresponds to the compromised ability of those sickled RBCs to transport oxygen around the body, hence the anemia. I kept waiting for my editor at Harvard University Press, Rachel Field, to say something, but she was happy to keep the working title.

GEN: When did you first encounter or remember learning about SCD?

Davies: That’s the thing. It was the first genetic disease I learned about in school in the U.K. some half a century ago! I remember sketching the healthy and diseased RBCs and learning about the sort of superpower that carriers of the sickle cell gene have against malaria. So many milestones in molecular biology revolve around the study of hemoglobin and SCD. Linus Pauling, PhD, dubbed sickle cell ‘the first molecular disease’ back in 1949. And yet, prior to the advent of CRISPR, the only effective therapy had been hydroxyurea, a generic chemotherapy drug. This community—an estimated 100,000 patients in the United States—has been waiting an eternity for something to get excited about.

GEN: You mentioned Victoria Gray. Is she a big part of the book? What makes her story so compelling?

Davies: Oh yes, absolutely! She was a guest on one of GEN’s virtual summits a few years ago. I met her in person a few months later and she invited me down to her home in Mississippi for an in-depth interview. We did that in her local church, which was special because I know how important her faith is. She opened up about the many episodes of discrimination that she experienced, something that is all too prevalent in the way people with SCD—almost exclusively persons of color—are treated in the medical system on both sides of the Atlantic.

Victoria deserves all her flowers. By going public with her story, she literally inspired other warriors to enroll in the CRISPR trial (sponsored by Vertex). I’m thrilled that she’s healthy and serving now as a patient advocate to raise awareness and help educate others with the disease. I also interviewed many other warriors in the book. I really hope readers will enjoy meeting LaRae, Danielle, Kwanzaa, Ray’Neshia, Jimi, and others. Every person’s story is unique and special in its own right.

GEN: Much of your book is spent detailing the story behind Casgevy. What was notable about that work?

Davies: Casgevy works not by fixing the SCD mutation directly but via a clever workaround: boosting the levels of fetal hemoglobin (HbF) to compensate for the inherited mutation in adult hemoglobin. The first inkling of that strategy dates back to 1948 and the clinical observations of a New York pediatrician named Janet Watson. Two decades ago, researchers made the key discovery that variants in a transcription factor called BCL11A influence HbF levels. It is great to see the scientists behind that fundamental discovery—Swee-Lay Thein, MD (NIH) and Stuart Orkin, MD (Harvard Medical School)—belatedly receive recognition in the form of the 2026 Breakthrough Prize.

I talk about the work at CRISPR Therapeutics and Vertex that led to the commercial approval of Casgevy. It’s impressive that Vertex has also driven the discovery of life-changing small-molecule drugs for cystic fibrosis, another classic genetic disease that also rose in frequency because carriers had a selective advantage, most likely against an infectious disease.

GEN: Many GEN readers will be broadly familiar with the story of SCD. Did you discover anything new or surprising in your research?

Davies: Hopefully a few surprises, yes! One is in regard to the first documented case in the United States—Walter Clement Noel, a dental student from Grenada, who was treated in Chicago in 1904. It was his case that was first documented in a medical journal in 1910. But obviously there were thousands of patients with SCD who reached the Americas during the Middle Passage. I spoke to a researcher at 23andMe who was an author on a major paper in Science two years ago analyzing the remains of some 30 enslaved African Americans at the Catoctin Furnace, an iron foundry in northern Maryland. She told me that forensic DNA sequencing revealed that three children buried there, dating back to the early 1800s, carried the SCD mutation.

I also interviewed the first patient to be cured of SCD via gene therapy more than a decade ago, a young Frenchman named Leeroy Tegar. Initially, his physician, Marina Cavazzana, MD, in Paris, didn’t think he’d want to talk to a journalist. But he did, with a big assist from Google Translate and Rodolphe Barrangou, PhD, the editor of The CRISPR Journal, who is French.

GEN: You also visited the site of Walter Noel’s grave in Grenada?

Davies: After dental school, Walter returned to his home on the Caribbean island of Grenada in 1907 and set up his own practice, only to die in 1916. His identity was uncovered decades after the famous 1910 medical journal paper by Todd Savitt, PhD, a retired history professor. A few years ago, I felt compelled to follow in Savitt’s footsteps, hiring a driver to take me from the capital of Grenada to Sauteurs, a town on the north coast of the island, where Noel is buried in a Catholic cemetery.

GEN: Despite the excitement over CRISPR and gene therapy, you depict a much darker side of sickle cell care. Tell me about Brittany Hightower.

Davies: Early on in my reporting, I watched some videos that had been live-streamed by Brittany Hightower, a 30-something sickle cell warrior in Texas. Brittany documented some distressing scenes at a major Dallas hospital, staff not wanting to care for her. In one viral video, two security guards informed her that she was being kicked out of the hospital—in the middle of a pain crisis. She died of pneumonia a couple of years ago.

I tracked down Brittany’s best friend and fellow sickle cell warrior, Kwanzaa, who ironically had taken part in the Lyfgenia gene therapy trial at NIH. Kwanzaa graciously shared Brittany’s final texts to her, sent just days before she died. I included them in the book as a poignant reminder that medical progress is one thing, but we can do so much better in educating medical professionals about this disease.

GEN: What impact will Casgevy and Lyfgenia have on sickle cell treatments in the long run?

Davies: We have to keep these launches in perspective. The experiences of the first cohort of patients taking these therapies have been amazing—almost all report no pain crises or hospitalizations or even the need for blood transfusions. Those that do typically had too much vascular damage before they received therapy. As Haydar Frangoul, MD, the physician who treated Victoria, says: ‘I can take the hammer away, but I can’t fix the wall.’

Remember this is ex vivo therapy, requiring months in hospital and a brutal chemotherapy regimen prior to therapy. The dream is to develop a much less complex in vivo gene therapy. Of course, even that will be of limited benefit to the millions of SCD patients across Africa, India and other parts of the world. I am optimistic that eventually scientists will develop a small molecule drug that can mimic the effects of Casgevy. Wouldn’t that be something?

GEN: The elephant in the room of course is that Casgevy costs $2.2 million, and Lyfgenia more than $3 million. What happens to patients who really need it but cannot afford the therapy?

Davies: True, the costs are very high, but that doesn’t appear to be the big stumbling block. Most private insurance companies and a majority of states in the U.S. are covering these therapies. $2–3 million in a one-time therapy is still good value compared to the costs of treating patients for recurring pain crises and organ failure over decades. The manufacturing process is also improving, which is helping to shorten the treatment timeline.

GEN: Thanks for speaking with me and congratulations, Kevin. Best of luck with the book!

The post The Saga of Sickle Cell Disease appeared first on GEN - Genetic Engineering and Biotechnology News.

Developing these models takes time and money, according to Nirrin Technologies CEO, Bryan Hassell, who told GEN, “They are built empirically, from large, designed experiments that span every condition the method will ever encounter. They are expensive to build, tied to the process and instrument they were built on, and to be rebuilt when the process, scale, or instrument changes.”

Pure component analysis

An alternative is the model-free approach “pure-component analysis,” continued Hassell. “In PCA each component has a known spectrum, and the measured spectrum is resolved into the concentrations of those components directly. There is no empirical model to develop and no DOE campaign behind it. A method built in development runs the same way in manufacturing, and on a different system at a different site.”

Hassell pointed to Nirrin’s new tunable laser near-infrared (TL-NIR) platform, which will be showcased at the Bioprocess International (BPI) East conference in Boston. to illustrate the potential benefits of pure-component analysis.

“It is a near-infrared measurement platform built around a tunable laser instead of a broadband lamp. The laser puts far more optical power into each individual wavelength, which gives a much higher signal-to-noise ratio than conventional NIR,” he explained. “Spectroscopic methods return spectra that must be interpreted through a model before anyone can act on them. TL-NIR returns concentrations. That is the number an engineer already makes decisions on, available in seconds or continuously, rather than a signal that needs deciphering first.”

But eliminating models is just one of the potential benefits, according to Hassell, who said “For protein analysis, a TL-NIR measurement is five times faster than variable-pathlength UV, and requires no dilution, no sample prep and no pathlength adjustment. The larger savings are upstream of that. Companies avoid the model-building campaigns that Raman and broadband NIR methods require, and they can bring in-house measurements that are currently sent out to HPLC, which removes both the cost per sample and the days of waiting for results.”

At present, five to 10 “top biopharmaceutical companies” use TL-NIR systems in process development, pointed out Hassell, and said the plan now is to raise awareness about the potential benefits of using the technology in commercial production.

“We are at the beginning of bringing this into manufacturing environments. These processes have been in place for a long time, and the industry will not convert to data-driven manufacturing overnight. We start in process development, where the technology is proven and validated and where transferability is demonstrated, and we are now working with key customers on manufacturing deployment from there.”

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The Minnetonka, MN-based supplier says its plant- and yeast-derived nutrients are intended for cell culture and microbial fermentation applications supporting vaccines, therapeutics, and other biologics. At BPI East, Nu-Tek will focus discussions with pharmaceutical leaders on product performance, media consistency, supply continuity, and the qualification of critical raw materials.

That emphasis reflects a broader challenge in bioprocessing: seemingly upstream choices in media composition can influence process robustness much later in manufacturing. Variability in complex raw materials can complicate process development and scale-up, while supply disruptions can force manufacturers to evaluate alternative sources or requalify components.

According to Joy Aho, PhD, Nu-Tek’s director of technical program management, “Bioprocessing relies on the control of critical raw materials from start to finish.” She added that the company’s products are designed to provide “quality, control, and customization options” for customers seeking to improve production performance while reducing risk.

Animal-origin-free materials can also help manufacturers simplify sourcing strategies where animal-derived components might create additional regulatory, traceability, or contamination concerns. Nu-Tek positions its peptones and hydrolysates as tools for reducing those risks without giving up the nutrient complexity often needed in demanding culture and fermentation systems.

During the meeting, Nu-Tek also plans to discuss its variability reduction program with teams looking to improve media consistency. The company also operates a purpose-built manufacturing facility dedicated to animal-origin-free peptones and protein hydrolysates.

For Nu-Tek, BPI East is less about introducing a single new product than about making the case that raw-material strategy has become a competitive part of bioprocess design. As biologics manufacturing grows more complex, suppliers are increasingly being asked to deliver not only performance, but also consistency, traceability, and dependable access.

The post Nu-Tek Brings Topic of Raw-Material Risk to BPI appeared first on GEN - Genetic Engineering and Biotechnology News.

The platform combines technologies from industry partners ATUM and Thomson Instrument to streamline cell line development, process scaleup, and manufacturing, he added.

“When developing life-saving therapies, speed and simplicity can make a significant difference,” continued McCool. “Many early-stage drug developers need a more efficient path to obtaining the GMP material required to reach the clinic. SmartScale was designed to help close that gap by providing a right-sized manufacturing approach that accelerates the journey to first-in-human studies.”

Developers increasingly seek approaches that enable earlier clinical evaluation of promising candidates while reducing development risk, timelines, and capital requirements.

“SmartScale is a stable pool-based manufacturing platform that can deliver GMP material for first-in-human studies in as little as eight months,” McCool said. “Our goal is to help customers reach the critical milestone of generating human clinical data that supports future regulatory and commercial decisions.”

GBI noted that the platform aligns with the FDA’s Operation TrialBlazer initiative, which seeks to accelerate the development of innovative therapies and modernize drug development pathways.

GBI partnered with ATUM to integrate ATUM’s Leap-In Transposase^® cell lines into its SmartScale platform, aimed at maximizing drug substance yield at smaller scales. ATUM brings cell line expertise, having enabled over 60 INDs across multiple therapeutic areas.

“The Optimum Growth^® Flask was designed to simplify scaleup while maintaining high-performance cell culture conditions,” said Sam Ellis, CEO of Thomson Instrument, about his company’s other contribution to the collaboration. “As part of the SmartScale platform, our technology helps streamline the transition from research and development into GMP manufacturing.”

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The instrument is the first benchtop-scale platform in Asahi Kasei Bioprocess’s VANTIJ family. The system extends the automation and operator-focused design principles of the existing portfolio while simplifying virus filtration processes, according to the company.

Its design accommodates workflows using 0.12 m² or 0.3 m² Planova 35N virus-removal filters. The VANTIJ simplifies small-scale Planova virus filtration while maintaining the process control and data-focused capabilities expected in biopharmaceutical development, explains an Asahi spokesperson.

Initially designed for gene therapy manufacturing, the new benchtop helps address the operational complexities associated with long production timelines, regulatory requirements, operator training, and therapy-specific needs, continues the company official, who adds that the system offers clear setup through a guided shadow-board layout, tool-free tube set installation and replacement, intuitive connection points, and recipe-driven software. It also enables batch reporting and supports the execution of key filtration processes.

“The biopharmaceutical industry continues to pursue more efficient pathways for bringing innovative therapies to patients,” said Chris Rombach, president of Asahi Kasei Bioprocess America. “The VANTIJ SU-VFC Benchtop reflects Asahi Kasei Bioprocess’s commitment to supporting manufacturers with solutions that simplify critical process steps.”

BPI East attendees can visit Booth 606 in Boston from September 22^nd to 25^th.

The post Asahi Kasei Introduces VANTIJ^® SU-VFC Benchtop Virus-Filtration System appeared first on GEN - Genetic Engineering and Biotechnology News.

The first clinical study to understand the potential effects of time-restricted eating in people with Huntington’s disease finds that time-restricted eating is feasible, safe, and linked to improvements in disease markers.

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In recent weeks, leaders of some of the biggest AI companies have warned that the very tech they are developing is dangerous. Last weekend, Anthropic CEO Dario Amodei argued that AI carries serious risk and that progress should be slowed. OpenAI CEO Sam Altman responded on X: “I agree with Dario that we need to pace the frontier.”

Those posts came a few days after the AI researcher Jacob Coxon announced that he was leaving a role at Anthropic, charging that neither it nor OpenAI (where he had also worked) was acting responsibly. “The people building AI earnestly believe that it could kill us all by the end of the decade,” he posted on X. Another Anthropic employee, Evan Hubinger, publicly agreed with him. “We really do earnestly believe AI could kill all humans!” he responded on X. “I personally think it is >10% within the next decade.”

One of the ways they fear AI might end us all is by somehow aiding the design, creation, and release of some kind of bioweapon. Let’s take a closer look at why.

A bioweapon might be a highly lethal virus that targets people according to their genes. It could be a fungus that wipes out a crop and causes food insecurity. Perhaps it would be a tasteless, odorless toxin that could be slipped into a region’s water supply, undetected.

The concern is that AI tools can be used to help generate agents like these. In 2022, researchers at Collaborations Pharmaceuticals found that it was remarkably easy to do so using an AI “molecule generator” they’d developed to find potential drugs for human disease. In less than six hours, the model generated 40,000 molecules with the potential to serve as chemical warfare agents. Some of them were designed to be even more toxic than known nerve agents. “Without being overly alarmist, this should serve as a wake-up call for our colleagues in the ‘AI in drug discovery’ community,” the authors wrote at the time.

It was a wake-up call for David Magnus, a professor of medicine and biomedical ethics at Stanford University, even though he had been assessing the risks associated with the misuse of medical science and biotechnology since the late 1990s. “That was very scary to me,” he says. “Of course, everything since then has just sort of blown up.”

Today, AI bots can answer questions on topics spanning all realms of science. Anyone can use large language models trained on the knowledge and experience of “almost every scientist who ever lived on this planet,” says Dunja Sabra, a biosecurity researcher at the University of Hamburg in Germany. Those models can provide instructions and video training on how to conduct experiments.

Combine that with advances in biotech that have made gene editing and synthetic biology tools much more accessible (the “DIY biology” movement has already enabled many people to set up labs at home), and you’ve got a potentially very dangerous situation. “The chances are that someone determined would succeed eventually,” Sabra says.

There are safeguards in place. People who want to build new genomes must typically order the pieces of DNA from companies that screen for suspicious requests. Responsible researchers put potentially risky research through rounds of analysis called “red-teaming,” in which independent scientists look for ways the work might be misused, and “blue-teaming,” where others come up with potential mitigations. And AI companies have tweaked their tools in attempts to prevent them from offering up scientific information that could be misused. But none of these protections are ironclad.

In a report published last week, Anthropic acknowledged that people had attempted to use its models to explore ways to make the chikungunya virus more transmissible, create a form of bird flu that is more dangerous to humans, and build an “atlas of venom toxin peptides,” among other things.

“We’ve got a constant back and forth,” says Magnus. “We have to build better surveillance and screening tools, [but] AI is really good at figuring out ways around them.” We’ll probably need to use AI to find ways to restrict the use of AI, he says.

I should add here that not all scientists agree on the level of risk. At a recent media briefing, some biologists at Imperial College London argued that AI tools just aren’t good enough to fully develop bioweapons, and that testing new pathogens requires difficult, time-consuming, human work. Some think the guardrails we have in place are sufficient.

And Wendy Barclay, a professor of infectious disease at Imperial, pointed out that, as things stand, the greatest risk of a pandemic isn’t from a bioweapon, but from pathogens that are already circulating. Take H5N1, the bird flu virus that has already killed millions of birds and spread widely through US dairy cattle; last month it was also detected in captive mink at a farm in Utah.

Sabra, on the other hand, likes to think five to 10 years ahead. Countries should be strengthening their health-care systems, preparing antidotes to known toxins, and stockpiling medicines, she says: “We need to be prepared.”

Kevin Esvelt, an MIT biologist who invented both technology to fast-track the propagation of a genetic feature through an entire population and ways to limit that technology, echoed these concerns in an X post on Wednesday, stating that a large language model had “disclosed a novel form of bioweapon that I hadn’t realized was possible.”

He added, “Please, for the love of God, children, the future of humanity, or whatever you consider holy, let’s err on the side of caution here.”

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

The Biotechnology Innovation Organization (BIO) is working to support Congress in ensuring our national health security by reauthorizing the Pandemic and All Hazards Preparedness Act (PAHPA) before year’s end. In a recent action, BIO joined over 80 other organizations and companies in signing a Sept. 14 letter urging congressional leaders to pass a PAHPA bill.

“This is a national security priority, an important way to protect Americans,” explains Phyllis Arthur, BIO’s EVP and Chief of Global Health. “PAHPA funds so many things that are essential for our national readiness and resilience. We are at a time when Americans care a great deal about what’s happening in terms of our nation being ready for known and unknown threats.”

Historically reauthorized on a five-year basis since it was initiated in 2005, PAHPA has not been reauthorized after the previous funding period ended in September 2023. While most PAHPA programs continue with short-term, temporary extensions, five-year funding is essential to incentivize research and development in medical countermeasures (MCMs), which can often take more than a decade to develop.

As a national security measure protecting civilians and the military, PAHPA has bipartisan support in Congress, and there is reason for optimism about reauthorization before the end of the year, according to Praneel Jadav, Manager, Infectious Disease Policy at BIO. “We commend the bipartisan champions in the House and Senate who are working to reauthorize PAHPA and we are committed to supporting their efforts,” he says.

While Congress has not yet put forth a bill for PAHPA reauthorization, it is expected to be aligned with earlier legislative proposals that  BIO would support, according to Jadav. He says BIO’s priorities for any PAHPA legislation are:

• Reauthorization of several key Administration for Strategic Preparedness and Response (ASPR) programs, including the Biomedical Advanced Research and Development Authority (BARDA), the Strategic National Stockpile (SNS), Project BioShield, and the Pandemic Influenza Program.
• Reauthorization of the Medical Countermeasure Priority Review Voucher (MCM PRV) program.
• Authorization of a Pathogen-Agnostic Viral Family program at BARDA.

Why ASPR matters

ASPR oversees most public health preparedness efforts and programs, including BARDA. BARDA works with industry to support the late-stage development of MCMs against chemical, biological, radiological, and nuclear threats, and emerging infectious diseases, all of which pose a real and present danger, Arthur explains.

“We know for instance that a flu pandemic is a threat every single year,” she says. “BARDA has been seeking to support companies working on vaccines against the various flu pandemic strains that pop up all over the world.”

ASPR also oversees the Strategic National Stockpile (SNS), a ready supply of MCMs ranging from smallpox vaccines to treatments protecting members of the military against nerve agents. Other vital ASPR programs include Project BioShield, which provides money and market incentives for private development of life-saving products that lack a commercial market.

Why the MCM PRV matters

An important part of the work PAHPA supports is industry-government collaboration to ensure drug companies develop new MCMs against potential threats and produce these drugs for stockpiling in the SNS.

“You can’t be standing around waiting for drug development in an emergency,” Arthur says. But since the hope is that we never need to use MCMs, regular market considerations would not encourage their development.

“We must have MCMs ready, though they often cannot be supported commercially,” Arthur explains. “Their marketplace is primarily government, and the U.S. government is the main global purchaser.”

Government support for this type of drug development is vital because most early research and development of MCMs is handled by small and mid-sized biotechs, with moderate budgets, Jadav notes.

“Anything we can do to show there is government support really helps these companies make a case with investors to continue funding innovative medical countermeasures that protect both civilians and the warfighter,” he says.

One mechanism to reduce the financial risks of developing a new MCM is the MCMPRV, a voucher that grants developers of MCMs priority Food and Drug Administration (FDA) review of a future drug candidate.

The faster time to market is a financial boost to drug developers, and MCM developers seeking capital can also sell the vouchers to other companies. While vouchers offer real value for drug makers, they cost taxpayers nothing.

Why viral families matter

Another key PAHPA initiative BIO wants to see is authorization of a dedicated Pathogen-Agnostic Viral Family program at BARDA. Examples of viral families include mpox and smallpox, which are both treated with one vaccine. We can more quickly achieve a range of treatments by developing vaccines or antivirals for other viral families—like the family that includes Marburg and Ebola, or the COVID-SARS-MERS family.

“This is more of a progressive method to address threats in emerging infectious diseases,” says Jadav. “It focuses research on medical countermeasures that address a whole host of viruses instead of doing a one bug, one drug approach.”

While BARDA has initiatives to encourage MCMs for viral families, a dedicated program would improve efficiencies in this area.

With PAHPA’s power to promote these essential health defense measures, BIO and its co-signers on the Sept. 14 letter to Congress see risks in delaying the legislation.

“Failing to reauthorize PAHPA now would have serious effects on our country’s economic wellbeing, national security, and health given the rapidly changing threat landscape,” the letter explains.

The post A national security priority: BIO pushes PAHPA reauthorization in 2026 appeared first on Bio.News.

The team carried out proteogenomic analyses of tumors from more than 100 HGG patients aged 0–40 years. Their multiomics analysis identified two AYA age groups with distinct molecular profiles and survival outcomes.

The researchers suggest that using the study results to guide clinical trial design and develop new therapies could advance more precise treatment strategies.

“Our goal was to understand high-grade glioma from infancy through young adulthood and identify tumor-related changes tied to outcomes such as survival,” said Pei Wang, PhD, professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai. “Because age and sex shape normal brain development, we wanted to separate features of the cancer from those associated with a patient’s developmental stage.”

The study was conducted by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), the Children’s Brain Tumor Network, and the Philadelphia Coalition for a Cure.

Wang, and Avi Ma’ayan, PhD, Mount Sinai endowed professor in bioinformatics and director of the Mount Sinai Center for Bioinformatics, are principal investigators of the Proteogenomic Data Analysis Center at the Icahn School of Medicine, part of CPTAC.

Wang is co-senior and co-corresponding author of the researchers’ published paper in Cell Reports Medicine, titled “Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and candidate kinase targets.” In their paper the investigators concluded, “This study provides an integrated multiomics analysis of HGGs across development, establishing a framework in which age and developmental context shape tumor biology.”

High-grade glioma is among the most aggressive primary brain tumors, with a five-year survival rate below 10%. Tumors in children differ markedly from those in adults, while adolescents and young adults remain especially understudied because their tumors do not fit neatly into either pediatric or adult disease. “High-grade gliomas (HGGs) in children and adolescents and young adults (AYA) exhibit distinct biology across the neurodevelopmental spectrum,” the authors wrote. “Differences between male and female patients, which influence both brain development and cancer biology, represent another underexplored dimension.”

Because age and sex shape normal brain development, the researchers sought to distinguish tumor-related molecular features from those associated with developmental stages. Working with CPTAC, the team profiled tumors—samples were collected through the Children’s Brain Tumor Network—from 112 patients aged 83 days to 40 years, measuring DNA, RNA, proteins, and chemical changes made to proteins after they are produced, including phosphorylation and glycosylation.

Those measurements were combined with data from 99 adult glioblastoma tumors and clinical and genetic information from a reference group of more than 5,000 people with high-grade glioma, to trace how tumor biology changes across the lifespan.

Using computational analysis and laboratory validation the team identified as potential treatment targets several kinases—enzymes that help control cell signaling—including CDK8, ATM, ATR, and LCK.

Studies showed that in tumor-derived cell lines, blocking these kinases through gene editing or drug treatment slowed growth when the corresponding kinase was most active. CDK8 emerged as a particularly notable candidate because it is less well characterized in high-grade glioma than established targets such as ATM and ATR. Analyses indicated that CDK8 suppresses oxidative phosphorylation (OXPHOS), a key energy-producing process that the study linked to more favorable survival. “Causal network analysis and cell line studies provide a rationale for personalized therapies targeting candidate kinases, such as CDK8,” the investigators noted.

By tracing molecular profiles continuously across age rather than sorting patients into established tumor subtypes the researchers identified a clear shift around age 26 years within an age range often grouped clinically as adolescents and young adults. The two study groups (adolescents aged 15 years to 26 years and young adults aged 26 years to 40 years) had distinct molecular profiles and survival outcomes and relied on different signaling programs.

Comparing tumors with normal brain tissue across the same age span sharpened the picture. Oxidative phosphorylation showed age- and sex-related changes in tumors that were not seen in normal brains, suggesting these differences arise from tumor processes rather than normal development.

About 27% of the proteins the team measured showed different age-related trajectories in male and female patients. A prognostic score established in earlier work was associated with outcomes in male patients but not in female patients. Glycosylation proved especially informative in male patients, with far more survival-associated features than in female patients. Protein-based grouping also revealed a previously unrecognized male subgroup with the poorest survival in the study, distinguished by immune signaling and features of the tissue surrounding the tumor.

“CPTAC allows us to examine the same genes across several layers of biology, from DNA and RNA to proteins and protein modifications,” said first author Nicole Tignor, PhD, assistant professor of genetics and genomic sciences at the Icahn School of Medicine “In this study, glycosylation captured aspects of tumor biology missed in other molecular data. It may be especially valuable for understanding differences between male and female patients in immune responses and, potentially, treatment response.”

Higher levels of infiltrating T cells were associated with better outcomes in female patients but not in male patients, while a pattern involving the immune checkpoint gene PDCD1, which codes the protein PD-1, was seen only in male pediatric and young adult patients. Because PD-1 inhibitors are already being studied in this population, the authors say the findings support further study of treatment strategies that account for these differences. “Our integrated analysis also revealed immune cell types associated with survival,” they noted. “T cell infiltration was linked with favorable outcomes in female PED/AYA HGG patients but not in male counterparts and correlated with PD-1 expression only in males, a pattern absent in adult tumors (>40 years),” the investigators stated.

They pointed out that that sex-related differences have emerged as an important determinant of immune response in glioblastoma, with evidence indicating that that male patients may exhibit greater sensitivity to the immune checkpoint blockade. “As PD-1 inhibition therapies are under active investigation in clinical trials involving PED/AYA HGG patients, our findings support the development of male and female-specific treatment strategies.”

The authors further noted that sample sizes are limited, which is a persistent challenge in rare pediatric cancers that is more pronounced when patient data are divided by age, sex, and tumor features. The team developed an analytic approach that uses molecular trajectories learned in one group to help interpret survival patterns in another. Even so, the team noted, some findings will need confirmation in larger studies, and targets such as CDK8 will require validation in animal models before clinical testing.

The mechanisms underlying the observed differences between male and female patients also remain to be defined. Nevertheless, the investigators concluded, despite limitations, “… our study advances understanding of the developmental patterns in male and female HGGs and identifies molecular and immunologic features with translational potential.”

Wang added, “Patient data are becoming increasingly rich, but they also reflect cancers arising at different ages and in different biological settings. How we account for that variation affects which biological signals we can detect. Analyzing tumors in their developmental context can help us make better use of these data and identify patterns that might otherwise be missed.”

The Children’s Brain Tumor Network and CPTAC are continuing to collect samples and generate data across pediatric brain tumors and other childhood cancers. The team will use those larger datasets to determine which patterns hold across cancers, which are specific to high-grade glioma, and which are most promising for therapeutic development.

The study’s proteogenomic datasets are publicly available through the NCI Proteomic Data Commons and the Children’s Brain Tumor Network, and the analysis code has been released openly.

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Available as a downloadable protocol, the workflow provides researchers with a ready-to-implement approach to automating organoid culture, helping reduce hands-on time and experimental variability while enabling more consistent, scalable generation of human-relevant research models and accelerating discovery, according to an official at Molecular Devices.

The workflow marks the first milestone in a strategic collaboration to automate STEMCELL’s portfolio of organoid culture kits on the CellXpress.ai system. By combining STEMCELL’s expertise in organoid biology with Molecular Devices’ automation capabilities, the companies aim to help researchers more easily adopt and scale human-relevant models, reducing barriers to implementation and accelerating research workflows in laboratories worldwide, explained Mary Duseau, president of Molecular Devices.

Under the collaboration, Molecular Devices develops and validates automated workflows, while STEMCELL provides tissue-specific science for performance criteria and cell-based functional characterization to support protocol development and validation.

“Organoids have the potential to give researchers a more human-relevant view of disease and treatment response, but their broader use depends on making these models easier to implement at scale,” continued Duseau. “This collaboration is an important step toward giving more scientists practical access to advanced cellular models while freeing them to focus on the biological questions that can inform the development of better therapies.”

The workflow reportedly enables automated culture, monitoring, and analysis of human intestinal organoids within a standardized process on the CellXpress.ai system. Researchers can implement the validated protocol as provided or adapt it to meet specific experimental requirements, providing flexibility for a range of organoid research applications, noted Allen Eaves, PhD, president and CEO of STEMCELL Technologies.

“This collaboration helps make advanced organoid workflows more accessible to scientists working across drug discovery, disease research, and translational biology,” he said. “Together, we’re enabling researchers to combine well-established organoid culture systems with automation, supporting the adoption of new approach methodologies (NAMs) and making it easier to generate reproducible results and scale their work as research needs evolve.”

The companies plan to evaluate additional organoid models and workflows for automation on the CellXpress.ai system, creating a portfolio of validated applications for drug discovery, disease modeling, toxicology, and translational research.

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Researchers led by Benjamin S. Freedman, PhD, at the University of Washington and University of Miami, report that human kidney organoids exposed to elevated glucose developed tissue-intrinsic inflammation and epithelial cell detachment, including detachment of podocytes, specialized cells essential for the kidney’s filtration barrier. The study, “Elevated glucose in kidney organoids induces tissue-intrinsic inflammation driving epithelial detachment,” was published recently in Stem Cell Reports.

“High sugar causes inflammation in these organoids even though they lack an immune system,” Freedman said. “This was unexpected and gives us a new way to think about how diabetes can affect kidneys and other organs.”

Diabetic kidney disease affects about 40% of people with diabetes and can progress to kidney failure due to persistently high blood pressure. Although current therapies can help control blood sugar and blood pressure, few treatments directly address the cellular damage that occurs in the kidney. The researchers set out to model that damage using human kidney organoids, which are generated from pluripotent stem cells through a stepwise differentiation process that recapitulates aspects of kidney development.

To mimic diabetic conditions, the team cultured kidney organoids in media containing different glucose concentrations. Organoids maintained in lower glucose conditions remained largely intact, but those exposed to higher glucose levels showed progressive morphological deterioration. Importantly, live/dead and lactate dehydrogenase assays suggested the changes were not caused by overt cytotoxicity. Instead, the researchers observed detachment of podocytes and tubular epithelial cells from the main organoid body, a phenotype reminiscent of changes reported in kidney biopsies and urine samples from patients with diabetic kidney disease.

Single-cell RNA sequencing pointed to activation of inflammatory pathways in the high-glucose organoids. MIF emerged as the top upregulated gene across the complete dataset, epithelial cluster, and podocyte subcluster, while TNF-alpha/NF-kB signaling was among the pathways enriched in epithelial and proximal tubule subclusters. Several pathway-level changes, including TNF-alpha/NF-kB signaling, also overlapped with transcriptomic data from human diabetic kidney disease biopsies. “Thus, our scRNA-seq analysis suggested that high glucose levels promote TNF-alpha and MIF expression, driving inflammation and podocyte injury,” the authors wrote.

The researchers then tested whether blocking these inflammatory pathways could blunt the injury phenotype. Inhibiting MIF with ISO-1 or TNF-alpha with etanercept protected organoids from podocyte injury under high-glucose conditions. MAPK pathway inhibitors also partially rescued podocyte morphology. These findings suggest that inflammation may be more than a secondary consequence of diabetic kidney damage.

The authors caution that further work is needed before these findings can be translated into patient therapies. The model required relatively high glucose levels to induce injury in the absence of TNF-alpha, and organoids lack a functional vasculature and immune system. Still, the study provides a controlled human platform for dissecting how hyperglycemia affects kidney cells and for evaluating potential anti-inflammatory strategies.

“While our findings suggest that inhibitors of MIF, TNF-alpha, or MEK can be used to intervene in this process, careful consideration and preclinical studies are needed to determine which of these treatment strategies is likely to be most effective,” the authors wrote.

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As he explained in a conversation with GEN this week,  “the question for me has been, what can technology do to accelerate getting medicines to patients a lot faster?” He and the Mithrl team believe that their artificial intelligence platform may be one of the keys. This week, the company announced a $20 million Series A funding round led by Obvious Ventures, with participation from Headline, AGI House, and several pharma executives, that will support the development of the second generation of Mithrl’s platform. The platform, dubbed Mithrl-1, comprises the company’s proprietary biomedical world model and an agentic harness for model routing, token optimization, and content orchestration. Mithrl is launching an early access program for the second-generation of the platform that will launch on September 21.

Mithrl’s platform combines validated biology curated from decades of peer-reviewed research as well as public and partnered datasets with agentic AI. Biopharmaceutical teams that deploy the company’s solution can combine that data, AI agents, and their proprietary data in their own environments. The platform cross-references data across disciplines to surface non-obvious connections using only published and verified data. Because the AI agents only reason over validated biology, rather than searching their way to answer from a broader pool of information, they require much less compute power to complete their tasks, according to the company. 

That assertion is supported by results from a recent benchmark analysis, shared by Mithrl, that showed that running its infrastructure used 45% fewer tokens than standard workflows running the same frontier base models without customization. Finally, when the system generates hypotheses, it includes details about the sources used as well as a confidence score that captures what the system read, how it got there, and how much to trust its output. 

Mithrl-1 is deployed in each client’s environment and harmonizes across existing frontier models. Each client’s implementation is then extended using their own proprietary data and pipelines. From there, teams can build and manage their own bespoke biomedical agents in-house. As new studies come in, Mithrl updates its knowledgebase and those changes are pushed out to customers on a regular basis giving them access to studies that are relevant to their work, and that could influence how they approach research questions. 

These kinds of capabilities are important as AI systems become more embedded in biotech and biopharma labs. “Every player in this category is racing to generate more raw hypotheses, faster. But the industry is cracking under the weight of hypotheses it can’t triage or validate,” said Adarsh, who also serves as the company’s CEO. Mithrl set out to answer a different question. “Which of these will actually hold up in downstream experiments, and ultimately in patients? The platform doesn’t guess. It reasons from trusted studies and each client’s in-house evidence the way a client’s best scientists do, and it shows its work every time.” 

To date, Mithrl’s platform has been used by several top-10 pharmaceutical companies, clinical-stage biotech companies, and genomics platform partners, according to the company. That list includes Elephas Biosciences, a company that develops an ex vivo tumor profiling platform. In April this year, the companies announced a scientific collaboration aimed at combining functional tumor profiling with AI-driven analysis to discover novel immunotherapy responses signals. The company could announce additional customer deals in Q4 of this year.

Some companies are already “AI-ready” which makes implementing Mithrl’s infrastructure more straightforward but most need some support to efficiently implement the company’s infrastructure, Adarsh says. “We have forward deployed scientists that go in, work with them, [help] them understand what knowledgebase does, and how we can make everything standardized.” 

As the AI market matures, it has also become easier to make the case for implementing AI and communicating their platform’s benefits. A year ago, “you kind of had to work a little bit to educate where the value is” but that has changed in recent months, Adarsh noted. “I think there is a systemic level of education that has gone on over the past 12 months, mostly led by Frontier Labs, which is good for us.” There are also management changes happening across the biopharma industry and those shifts seem to be driving interest in onboarding AI, Adarsh said. He told GEN that he has noticed an uptick in conversations with company executives who “have a notion of the value that they are looking for” and are interested in understanding how Mithrl’s platform can help them get there.

So far the company’s tools seem to be making their mark on the industry. According to Mithrl, discoveries powered by its platform have contributed to over half a dozen customer-owned patent filings. It also claims that its biomedical world model delivers 16x more primary evidence per answer than frontier models alone and scored 0.96 for scientific correctness in expert-rated biomedical benchmarks, compared to 0.6 without its platform. 

These proof points are helpful in a crowded market of AI-focused companies targeting drug discovery. Adarsh acknowledged the hype while discussing what sets Mithrl apart from other companies in the space. “Our north star is to be able to give scientific value and uniqueness to our partners,” he said. “What truly draws the revenue, and the topline for pharmaceutical companies, is uniqueness” specifically “patents.” He pointed to the platform’s contributions to multiple patents noting that customers have highlighted the competitive edge it gives. Those outcomes are “what differentiates us.”

And those outcomes, at least in part, are driving growing interest in the company’s platform. Adarsh told GEN that the current fundraising round was motivated to an extent by greater customer demand as well as a need to expand its capabilities. To the end, the new funding will support further development of the underlying biomedical world model as well as allow Mithrl add to its headcount, which currently stands at about 30 people. “In the order of priority, we have more demand to do deployments of our platform within big organizations, which obviously requires headcount,” Adarsh said. “Second is expansion across therapeutic areas.” The primary focus for now will be on disease areas that its target customer base works on including, immune-related diseases, oncology, diabetes, metabolic disease, and cardiovascular disease. 

If all goes well, developing new medicines “won’t take 15 years” but “five years,” Adarsh said. “That is the personal motivation that led us to create Mithrl and that’s the path we’re on.”

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As part of the collaboration, Sartorius will equip NIBRT with its Pionic technology—an end-to-end modular cGMP platform for integrated continuous bioprocessing with advanced analytics and digital tools. Through the collaboration, the new facility is expected to provide more than 1,000 scientists, engineers, and students each year with hands-on experience in intensified upstream and downstream processes designed for efficiency, flexibility, and sustainability.

René Fáber, head of the bioprocess solutions division and member of the executive board at Sartorius, pointed out that biopharmaceutical manufacturing is undergoing a major shift from batch processes toward more efficient, continuous processes.

“While technological innovation is the first step, training current and future engineers and operators is critical to making the change a reality,” he said. “Our partnership with NIBRT underscores Sartorius’ commitment to building global capabilities and accelerating the adoption of innovative and sustainable bioprocessing technologies.”

“This collaboration marks a significant step in advancing workforce training and supporting the transition toward intensified and connected manufacturing,” added Darrin Morrissey, CEO of NIBRT. “By integrating the Pionic platform into our training facility, we will give biopharma professionals the chance to gain first-hand experience with cutting-edge technologies that drive process efficiency and performance.”

The Process Intensification Training Center will become a key element of NIBRT’s global training and education network, serving industry professionals and academic partners in Ireland, Europe, and worldwide, noted a NIBRT spokesperson. Beyond training, the center will also enable collaborative research and pilot-scale demonstrations, strengthening the global biomanufacturing ecosystem, said the center official.

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The collaboration will focus on the translation of GenomeFrontier’s manufacturing process to the Cell Shuttle, with an emphasis on supporting transfection unit operation using Cellares’ integrated electroporator. The partnership marks Cellares’ first development collaboration in Asia and is intended to support GenomeFrontier’s U.S. clinical initiative as it advances GF-CART01.

GenomeFrontier is developing GF-CART01 for B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, primary mediastinal large B-cell lymphoma, and high-grade B-cell lymphoma. The company reports that it has demonstrated promising clinical data in Taiwan and is now recruiting for a Phase I clinical trial in the U.S.

“As we advance GF-CART01, it is important that our manufacturing strategy can support both clinical development and future scale,” said Sareina Wu, PhD, founder, CEO, and CSO of GenomeFrontier. “Our virus-free approach is central to the development of GF-CART01, and this collaboration with Cellares allows us to evaluate how that process can be translated to an automated manufacturing platform as we expand our clinical development in the U.S.”

“GenomeFrontier’s approach reflects the increasing complexity of next-generation cell therapy manufacturing,” added Fabian Gerlinghaus, co-founder and CEO of Cellares. “The Cell Shuttle is built to automate complex processes, including electroporation-based workflows, with the scalability and reliability needed as therapies advance through clinical development.”

Autologous CAR T manufacturing remains labor-intensive, variable and difficult to scale, creating challenges for clinical development, manufacturing reliability, cost, and ultimately patient access. The Cell Shuttle is an end-to-end automated cell therapy manufacturing platform designed to improve the scalability and reliability of autologous cell therapy manufacturing, according to Cellares.

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Tests in mouse models of STm-induced colitis showed that the prophage-encoding bacterium colonized the gut, produced high levels of lytic phage and protected mice from subsequent oral salmonella infection, improving survival. The team believes their results represent a step toward the development of new weapons against different diseases.

“Eventually, in the future, this could be used to treat other diseases,” said Rogerio A. Bataglioli, PhD, a postdoctoral fellow in the Department of Biological Sciences. “It’s not about replacing antibiotics but having one more option on the shelf to fight infections.”

Hsu is senior and co-corresponding author, and Bataglioli first and co-corresponding author of the researchers’ published paper in Nature Microbiology, titled “Prophage-encoding engineered bacteria enable prophylactic lytic phage therapy for enteric infection in mice.” In their paper the authors wrote, “In this study, we show that a nonpathogenic E. coli gut  bacterium can be engineered to produce an obligately lytic antipathogen phage, and the application of this lyto-lysogen before oral STm infection can improve survival in mouse models and reduce intestinal colonization of the pathogen.”

The mammalian gut microbiome is teeming with a delicate balance of bacteria and the bacteriophage viruses that keep them in check phages. Each bacterial species usually has its own set of phage partners.

When bad bacteria enter the gut microbiome ecosystem there are typically no phages present, allowing the bacteria to cause mayhem. By the time the host is sick, it is too late for phages, and they’ll simply reach a balance with the bad bacteria. Hsu said phage therapy, the use of phages to treat bacterial infections, is particularly hard to make successful for treating intestinal pathogens. “Phage therapy is a promising antibacterial approach but it has limited efficacy against enteric bacterial infections, such as Salmonella enterica Typhimurium (STm),” the authors wrote in their paper.

This coexistence makes establishing the high phage-to-bacteria ratio needed to treat intestinal infections hard to achieve. “That’s extremely challenging to achieve in your gut,” Hsu said. “And then once you have a bacterial infection in your gut, a lot of times it’s just not even accessible to phages. It’s already hidden away in the mucosa or cells of your body; it’s not just free flowing to where the phages would be able to access them.”

But what if the phages in the gut could prepare for the orally ingested pathogen and strike it down as it enters the gut, negating the need for a battle? “… We hypothesized that establishing high concentrations of a pathogen-targeting phage in the gut before infection would prophylactically protect against future infection,” the team further wrote.

For their study they engineered a nonpathogenic E. coli bacterium to encode a prophage that produces lytic phages that only infect the target STm bacterium. Usually, this type of Salmonella phage remains dormant in the Salmonella bacterial genome, but Hsu’s team made several genetic modifications so that the phage is carried by E. coli. Once released into the gut, the phage targets and kills the Salmonella by lysis. This process rapidly increases the number of phages to fight the bacteria. The researchers coined this new type of phage-bacterial combination a “lytic phage-producing lysogen,” or “lyto-lysogen.”

Salmonella can typically detect phage DNA produced by non-Salmonella bacteria and prevent it from replicating. But in this case, the researchers were able to disguise the phage. “We were able to trick the Salmonella bacteria into thinking the phage from E. coli was ‘not foreign’ by adding a Salmonella gene into the E. coli genome,” Bataglioli said. “A phage that comes from our E. coli can infect Salmonella, can propagate easily in Salmonella, lyse it, and then all the phages that are produced from Salmonella can just keep replicating.”

This rapid reproduction eventually leads to the eradication of the infection from the gut. “What happens is that this good bacteria, the E. coli, produces all this antipathogen phage, and there is now a protective lining so that when Salmonella comes in, just after passing through the stomach and at its weakest point, it meets this high, killer density of phages,” Hsu said. In their paper the authors further noted, “Within the context of the mouse model of STm infection that we use here, we found that this prophylactic application of prophage therapy was superior to its therapeutic application post infection, and superior to the prophylactic or therapeutic application of free phage.”

The researchers say they targeted Salmonella because the pathogen has high global disease burden, and can be deadly in the elderly, children, and those with HIV. The bacterium also has a high prevalence of antibiotic resistance, and has been upgraded to a high-priority pathogen by the Centers for Disease Control and Prevention.

The researchers believe their work also has strong implications for other illnesses. “We’re starting off with Salmonella, but expanding, obviously, with the correct adaptations to target other diseases; other bacterial pathogens, would be an interesting route to explore,” Bataglioli said. The team further noted, “Collectively, our work shows that the lyto-lysogen strategy is a feasible prophylactic approach and represents an advancement in how phage therapy is conventionally conceived.” Hsu added, “We have a framework in place that shows that we could potentially put other phages in there and target other bacteria.”

Bataglioli plans to continue his bacteriophage research with the School of Chemical Engineering at the State University of Campinas in São Paulo, Brazil, in the fall.

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The team, headed by assistant professor Min-Jue Xie, PhD, at the Division of Development of Mental Functions, Research Centre for Child Mental Development, suggests that the results offer insight into how brain changes may contribute to ADHD and informing future treatments.

“This is basic research and will not immediately lead to a new treatment,” Xie acknowledged. “However, it provides important clues for understanding how dopaminergic dysfunction may contribute to ADHD. In the future, these findings may help develop new therapeutic strategies targeting D2R function and striatal dopamine signaling, especially for treatment-resistant ADHD.”

Xie is first and corresponding author of the researchers’ published paper in Neuropsychopharmacology, titled “Deletion of N-ethylmaleimide-sensitive factor in dopamine D2 receptor-expressing cells impairs striatal development and dopaminergic function and induces ADHD-like behaviors in mice.”

ADHD is a neurodevelopmental disorder that can affect attention, activity levels, and impulse control, with symptoms often beginning in childhood and sometimes continuing into adulthood. Although the exact causes of ADHD are not fully understood, changes in the brain’s dopamine system have long been linked to the condition. Dopamine is a chemical messenger that helps brain cells communicate and plays an important role in movement, motivation, and behavior.

While dopamine-related changes have been associated with ADHD, it remains unclear how the brain cells that respond to dopamine are maintained and how their disruption may contribute to ADHD-related behaviors. This is particularly relevant to dopamine D2 receptor (D2R)-expressing cells, which are found in the striatum, a brain region involved in movement and behavioral control. Understanding what helps these cells develop and function normally could provide new insights into the biological processes involved in ADHD. “Although D2R has been extensively studied, the upstream mechanisms regulating its function and localization remain unclear,” the authors wrote.

Against this backdrop, a research team from Japan, led by Xie, set out to investigate the role of NSF in these dopamine-related brain cells. NSF regulates membrane fusion, helping brain cells release chemical messengers and move proteins within their membranes. “NSF dysfunction is implicated in neuropsychiatric disorders, with reduced expression in autism spectrum disorder (ASD) and schizophrenia and aggregates in Parkinson’s disease,” the investigators noted.

“The motivation for this study came from previous findings suggesting that NSF may be involved in neurodevelopmental and neuropsychiatric disorders,” Xie explained. “NSF was known to interact with D2R; however, the role of this interaction in vivo remained unclear. Because ADHD is thought to involve reduced striatal dopaminergic function and D2R dysfunction, we hypothesized that NSF may be important for maintaining D2R-expressing neurons and dopaminergic function. This led us to initiate the present study.”

For their study the team created knockout mice in which NSF was removed specifically from D2R-expressing neurons. “… we generated D2R-specific Nsf conditional knockout (Nsf ^f/f;D2R-Cre) mice to examine NSF function in D2R-expressing cells in vivo,” they explained. They then studied the animals’ brain development, dopamine levels, and behavior. The team also tested whether drugs that affect dopamine signaling could reduce the behavioral changes seen in the modified mice.

The loss of NSF affected the developing brain, resulting in fewer dopamine D2R-expressing cells, increased early developmental cell death, and a smaller striatum. The mice also had markedly lower dopamine levels in this brain region. Together, these findings suggest that NSF helps maintain dopamine-related cells and supports normal development and dopamine function.

The brain changes were accompanied by ADHD-like behaviors. “Nsf ^f/f;D2R-Cre mice exhibited attention-deficit/hyperactivity disorder (ADHD)-like behaviors, including hyperactivity and impulsivity,” the team reported. The knockout mice were more hyperactive than control mice and showed more impulsive-like behavior in a test that measured how quickly they jumped from an elevated platform. By the end of the seven-minute test, 86% of the experimental group mice had jumped, compared with 31% of the control group mice. “These findings indicate that a reduction in D2R-expressing cells coincides with ADHD-like behaviors, suggesting a link between D2R dysfunction and these abnormalities.”

The researchers then explored whether these behaviors could be reduced by changing dopamine signaling. Methylphenidate, a medicine commonly used to treat ADHD, did not significantly reduce hyperactivity when given alone to the modified mice. However, when it was given together with quinpirole, a drug that activates D2R, the mice became less hyperactive and showed less impulsive-like behavior. During the seven-minute test, the proportion of knockout mice that jumped fell from 78% without treatment to 11% after the two drugs were given together. “Combined administration of methylphenidate and a D2R agonist, quinpirole, alleviated both behaviors, suggesting a potential complementary approach for ADHD treatment,” the investigators wrote.

“This study supports the translational relevance of the Nsf ^f/f;D2R-Cre model for ADHD and indicates that targeting D2R dysfunction, particularly in treatment-resistant ADHD, may be a promising therapeutic strategy.”

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Multiple cameras tracked a mouse as it wandered around a small arena. A computer charted its position and speed, leaving Pong-like traces on a monitor. 

The reason to watch this rodent so carefully? Nearly half its brain volume had been replaced with human cells.

The effort to mix the brain tissues of distant species is being reported today in the journal Nature by a team at Stanford University, led by neuroscientist Sergiu Pașca. 

Pașca’s group previously showed that human brain “organoids”—small blobs of neural tissue—could survive, and even function, after being injected into the heads of baby rodents.

Now, Pașca has taken things a step further by genetically modifying mice so their brains don’t fully develop in the first place. These modified mice are missing most cells of both the cortex and the hippocampus, two key brain areas.

That creates much more room for the human cells to take hold, he says. “Human cells that are placed in these animals will divide, will grow, and within a few weeks to a few months they will take most of that space,” he says. Pașca says one surprising discovery is that the mice lacking brain tissue seemed fairly normal—they walked around and squeaked. But they did have memory problems. In a maze test, they couldn’t remember what parts they’d explored. 

The mice with the added human cells, by contrast, performed better on the maze test. That means the human tissue is playing some role in the animals’ cognition.

Pașca believes what he is calling “xenocortical mice” could be useful in studying brain injuries. However, the report is also a dramatic demonstration of “the combined power of genetic engineering and stem-cell technology to reshape biology,” says Carsten Charlesworth, a scientist who works in a different Stanford lab and was not involved in the research.

Already, brain organoids are being tested in labs to see if they can be connected to computers to play video games. Other scientists have proposed using them like replacement parts to treat stroke victims. 

“What’s most remarkable to me is the extent to which human neural tissue introduced after birth grew and connected with the mouse nervous system across a species barrier,” says Charlesworth. “As these technologies advance, they’ll increasingly force us to challenge our traditional assumptions.”

Last year, Pașca convened a group of ethics experts to study the implications of neural organoid technology, including the odds that an animal could develop human consciousness and the risk that “organoid therapy clinics” might offer scam treatments to desperate patients.

For now, he says, he’s not concerned that the rodents have any type of human cognitive capacities. That is because their brains are relatively tiny and the evolutionary distance between man and mouse is so great. 

But that’s also why Pașca says this type of experiment should not be carried out on higher species: They could end up with large volumes of functioning human brain tissue, potentially blurring the cognitive boundaries between people and animals. 

Pașca specifically cautioned against adding human brain organoids to a monkey engineered to lack a cortex.

“One of the things that I see as a very clear red line is doing this experiment in a primate,” he says. “I don’t think that is justified at this point in any way.”

At least, that is according to researchers at the Manipal Academy of Higher Education in Karnataka, India, who argue in a new review that developers struggle because they treat manufacturing, analytics, and regulatory compliance as separate issues.

“Historically, the field has tackled these problems separately: one group focused on CAR T manufacturing, another on viral vector production, and another on logistics or regulatory strategy, rather than treating the whole product lifecycle as a single connected system.

“Our review argues that scalability must be built in from the start, using lifecycle-oriented tools that allow manufacturers to embed flexibility into the process from early development through commercial-scale production, rather than trying to bolt scalability on afterward, once problems appear,” study co-author Sachin Dattram Pawar, PhD, tells GEN.

The key, Pawar and colleagues suggest, is to treat all parts of CGT production as a single, unified process designed with scalability in mind.

“The idea is to stop treating early development, scale-up, and commercial manufacturing as separate problems and instead manage manufacturing knowledge continuously across the product’s lifecycle,” he says.

The lifecycle approach is also in keeping with trends in bioprocessing technology development, Pawar says, pointing to decentralized systems like the CliniMACS Prodigy or Lonza Cocoon platforms as examples.

“The approach would involve closed and automated manufacturing systems, real-time process monitoring, advanced analytics, digital tools, scalable cell and vector platforms, and robust cryopreservation and cold-chain infrastructure.

He adds, “Emerging approaches, such as digital twins, AI, allogeneic and iPSC-derived platforms, and improved vector production technologies, could further enhance scalability and consistency.”

In addition, treating manufacturing as a single process would also be a better reflection of the complex interactions that take place between unit operations, Pawar says, citing cell culture systems as an example.

“Switching from one to another can simultaneously alter product yield, purity, and even cell behavior, which in turn has knock-on effects on analytics and regulatory submissions.”

Regulations

A lifecycle-based view of manufacturing also fits with evolving regulations, according to Pawar, who points to the development of “concrete regulatory mechanisms” as evidence of growing support for the approach.

“ICH Q12 provides tools such as established conditions (ECs) and post-approval change management protocols (PACMPs) to help manufacturers manage process changes based on risk and accumulated knowledge.

“Likewise, the FDA’s flexible CMC approach for CGTs also supports greater flexibility during development, while the agency’s RMAT designation and the EMA’s PRIME scheme encourage early regulatory engagement. Overall, regulators are moving toward a more risk-based, lifecycle-oriented approach that supports innovation while maintaining product quality and patient safety,” he concludes.

The post Lifecycle Approach Could Solve CGT Scale-Up Challenges appeared first on GEN - Genetic Engineering and Biotechnology News.

In a recent paper, researchers from the University of Cambridge, Eindhoven University of Technology, and Merck identified solubility differences among commonly used antibodies that ranged from approximately 7-fold to 200-fold. The differences came down to molecular specificity and the complexity of the antibody-excipient interactions. By understanding these indicators and their effects, biomanufacturers can design mAb formulations using a more predictive, rational design approach.

A team of eight, including first author Zexiang Han, a PhD candidate in the Knowles lab; and senior authors Tuomas Knowles, PhD, professor; and Pietro Sormanni, PhD, all of the University of Cambridge, analyzed the effects of four common pharmaceutical excipients (histidine, sodium chloride, arginine, and sucrose) on the solubility of a panel of therapeutic immunoglobulin G (IgG) antibodies using a high-throughput droplet microfluidic platform. They determined that excipient-mediated solubility depends strongly upon the antibodies themselves, and that solubility “can be quantitatively linked to specific molecular features derived from sequence and structure.”

For example, when looking at the solubility of 1 mg mL⁻¹ cetuximab in the presence of each of the four excipients, they reported that as excipient concentration increased, greater percentages of polyethylene glycol (PEG) crowder were needed to cause mAb precipitation. That was true for each of the excipients.

The scatter plots in the paper showed the relative concentrations of each excipient needed to meaningfully shift the solubility boundary. The histidine plot, for example, stops at about 35 mM, while the plot for sucrose stops at about 500 mM. For cetuximab, a relatively low concentration of histidine shifted the boundary, while a significantly higher concentration of sucrose was needed to cause a similar shift. The contrast among the various excipients, given the same antibody and same concentrations of PEG, underscores that the shifts were caused through molecularly specific interactions between the antibody and the excipient rather than by PEG’s excluded volume effect (i.e., crowding).

More specifically, they noted:

• “Histidine stabilization is fundamentally polar, correlating with antibody dipole moments.
• “Sodium chloride operates via nonspecific electrostatic screening to suppress self-association in low-pI variants [those in which the pI—the isoelectric point—is below that of the pH and have no charge].
• “Arginine efficiency reflects a competitive tradeoff between electrostatic screening and chaotropic effect.”

The takeaway, they reported, is that “formulation additives do not exert universal actions.” Instead, common excipients behave differently with different molecules. This work, therefore, provides “a mechanistic, physics-based framework that can support the rational design and optimization of antibody formulations,” the team pointed out.

The post Choice of Excipients Dramatically Affects Antibody Solubility appeared first on GEN - Genetic Engineering and Biotechnology News.

Deepanshi Rajput, a doctoral student in biotechnology, and Kashyap Kumar Dubey, PhD, associate professor in the School of Biotechnology at Jawaharlal Nehru University in India, studied Streptomyces toxytricini, a filamentous soil bacterium that naturally produces lipstatin. Lipstatin is especially interesting because it is the natural precursor of orlistat, an anti-obesity drug that works by inhibiting enzymes involved in breaking down dietary fats.

The team grew the bacterium under a spectrum of lighting conditions, including red, green, indigo, blue, yellow, violet, orange, and white light, with darkness serving as a control. What happened under red illumination stood out.

Lipstatin production reached roughly 6 g/L under red light, compared with about 1.2 g/L under white light and just 0.02 g/L in darkness. That translates to roughly a five-fold improvement over white light and about a 300-fold jump over the dark control.

Light was not merely changing how much of the compound the bacteria produced. It was also changing how they physically grew. Microscopy revealed that the bacteria formed dramatically smaller, looser structures under red illumination. Pellets averaged about 81 µm across, compared with roughly 333 µm under white light and 785 µm in darkness.

That architectural shift could matter in industrial fermentation. Dense clumps of filamentous bacteria can hinder the movement of nutrients and oxygen through a culture. Smaller, more dispersed structures might improve mass transfer and create conditions that favor production of secondary metabolites, such as lipstatin.

As the authors reported, their results show that “light acts as an important environmental factor” influencing both the morphology and metabolism of S. toxytricini. A search of the bacterium’s proteins also uncovered two putative bacteriophytochromes—possible red-light-sensing proteins that could help explain how the organism detects illumination.

But the biological mechanism remains unresolved. The researchers stressed that “a direct causal link cannot be established” between the altered pellet structure and increased lipstatin production from the current experiments alone. Functional studies of the suspected photoreceptors, molecular profiling, and validation in larger bioreactors will be needed.

Still, the results suggest that fermentation facilities might eventually gain another surprisingly straightforward control dial. Rather than modifying the microbe itself, a manufacturer could potentially influence what it produces simply by illuminating the bacteria differently—a “useful, non-invasive parameter” that the researchers argued deserves further investigation.

The post Red Light Supercharges Anti-Obesity Drug Precursor appeared first on GEN - Genetic Engineering and Biotechnology News.

Now, a new paper describes a novel genome engineering method, prime assembly, that allows long DNA fragments to be integrated into precise and programmable target positions within living cells. This approach, which leverages CRISPR-targeted dual flap synthesis, may allow for the development of universal gene therapies.

This work is published in Nature in the paper, “Targeted genomic integration and rearrangement using prime assembly.”

Prime assembly builds upon the techniques of prime editing, a technology that allows for precise yet small insertions, deletions, and base swaps. The new method, the authors note, “enables RNA-programmable site-specific integration of single or double-stranded DNA fragments. Unlike homology-directed repair, prime assembly is similarly active in dividing and non-dividing cells.”

The team applied prime assembly to perform targeted exon recoding, transgene integration, and megabase-scale rearrangements, including at therapeutically relevant loci in primary human cells.

Prime assembly’s single step process writes in new DNA flaps to specific locations in the genome. The flaps serve as tethers designed to grab onto DNA fragments with matching ends. The precisely assembled DNA inserts, which can be one or more gene-sized DNA pieces, become large permanent edits.

“By using prime editing to write in one flap per strand of the genome, the method controls exactly where the DNA replacement starts and ends,” explained Daniel Bauer, MD, PhD, director of the Gene Therapy Program at Boston Children’s Hospital. “Because the method is based on prime editing, it is much less likely to cause off-target effects compared to other gene editing methods.”

One such off-target effect is the potential for toxicity. Untargeted insertion methods can turn on the wrong genes in the wrong context, leading to potentially cancerous outcomes, whereas prime assembly’s targeted insertion approach circumvents the risk. Prime assembly also does not rely on DNA double strand breaks or DNA double strand donors, both of which can be toxic and cause unwanted cell stress. And while other gene editing methods are mostly limited to dividing cells which are rare in the body and more susceptible to unwanted DNA changes, prime assembly works in nondividing cells.

Building on this milestone, the team is looking to further investigate the molecular mechanisms which would allow them to engineer even more efficient and precise systems. As they fine tune their approach, they hope this technology will have downstream impact in the clinic. With the ability to correct multiple mutations at once, this technology could lead to generalizable solutions for treating genetic disorders.

“We’re working to improve the delivery of the prime assembly components to disease-relevant human cells in vivo, such as hematopoietic stem cells for blood disorder therapies,” said Bauer. “We’re also exploring a number of applications of prime assembly to deliver genetic payloads as mutation-agnostic therapies to restore gene control for devastating inherited human diseases with unmet clinical need.”

The post Prime Assembly Expands Genome Editing with Precise, Large-Scale DNA Integration appeared first on GEN - Genetic Engineering and Biotechnology News.

Now, researchers at the Salk Institute have created what they describe as the first microprotein atlas of the human frontal cortex with and without Alzheimer’s disease. The study, “A microprotein atlas of the human frontal cortex in Alzheimer’s disease,” was published in Nature Aging. The resource integrates transcriptomics, mass spectrometry, and deep-learning-predicted spectra across postmortem brain samples to identify microproteins that have been overlooked in standard protein catalogs.

“We still do not fully understand the molecular mechanisms of healthy aging, and that is especially true for microproteins, which have been inadvertently overlooked for decades,” said senior and co-corresponding author Alan Saghatelian, PhD, professor and the Dr. Frederik Paulsen Chair at Salk, in a press release. “Our atlas allows scientists to systemically investigate microproteins in aging and neurodegeneration, which should bring us closer to understanding and tackling diseases like Alzheimer’s or Parkinson’s.”

Saghatelian told GEN the work began with a basic limitation in how proteomes are annotated. “Every reference proteome is built on gene models that exclude smORFs by construction. So the first motivation was straightforward: build a search database that can actually see these sequences, and point it at the deepest human brain proteomics data that exists.”

The atlas was built using data from hundreds of postmortem human frontal cortex samples from individuals with and without Alzheimer’s disease, including samples made available through the Religious Orders Study/Memory and Aging Project cohort. The team analyzed existing native transcriptomic and mass spectrometry data with custom computational tools, including ShortStop, an AI-powered microprotein-finding tool developed in Saghatelian’s lab.

“We were able to take all these technologies and tools and reapply them to existing data from nearly 500 brains to find new microproteins,” said first and co-corresponding author Brendan Miller, PhD, a postdoctoral researcher in Saghatelian’s lab. “We were able to create an entirely new database that researchers can download and use to better interpret functions of genes.”

In total, the researchers identified 1,067 previously uncharacterized microproteins absent from reviewed UniProtKB entries, supported by high-confidence spectral support, according to the paper. Some of these microproteins were expressed differently in Alzheimer’s disease samples compared with non-Alzheimer’s samples, and the paper reports that Alzheimer’s disease cells tended to show higher overall microprotein expression.

The investigators then focused on microglia, which are known to change with aging and neurodegeneration. Their analysis highlighted a small open reading frame at the MKKS locus encoding a 63-amino-acid microprotein that appeared to be the predominant translation product at that locus and is downregulated in Alzheimer’s disease. When the researchers knocked out the microprotein-making gene in microglia, mitochondrial respiration was impaired, suggesting a role for the microprotein in microglial bioenergetics.

The MKKS finding also underscored a broader issue with relying only on canonical protein annotations. “The general implication is uncomfortable: the most abundant and most tissue-relevant protein product at a locus can be the one that isn’t annotated,” added Saghatelian.

He also cautioned that not every microprotein identified in the atlas should be assumed to be functional. “There are two ways to read an expressed microprotein. It may be a marker—evidence that its gene’s transcription or splicing is disrupted—without the peptide itself doing anything. Or it may be a bioactive molecule with biology distinct from the canonical product at that locus.”

The findings point to a possible connection between microproteins and immune cell dysfunction in Alzheimer’s disease. “There is sometimes an assumption that we know everything about our genome, and we know all the genes our cells can make—that’s just not true,” Saghatelian said. “What we know is constantly expanding, and this atlas makes it that much easier to study microproteins in life science research.” Beyond Alzheimer’s disease, the publicly available atlas could serve as a framework for mapping microproteins in other brain regions, tissues, and disease contexts.

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Last year Ruxandra Teslo, a policy analyst who focuses on clinical trials, posted an idea for supercharging medical AI systems: Use data from failed biotech companies.

By bidding at their bankruptcy proceedings, she proposed, it might be possible to obtain detailed regulatory filings, manufacturing strategies, and safety data—types of information usually considered trade secrets. She called these documents “biotech’s lost archive” and said they could be used to help train AIs that would act as powerful copilots in the often opaque drug approval process. 

Today the OpenAI Foundation, the nonprofit parent of OpenAI, said it would fund her idea as part of a new effort it calls Public Data for Health, which aims to help artificial intelligence make big leaps in medicine by paying to create “high-quality scientific datasets.”

The basic idea is that AI isn’t going to be capable of making important breakthroughs in curing disease unless researchers can feed the models much more information than they have so far. 

“Everyone is recognizing that data is the biggest bottleneck in successfully applying AI to biology,” says Morgan Levine, a former vice president for computation at Altos Labs, a longevity company.

In its initial round of data grants, the OpenAI Foundation also announced that it would give $40 million to a program to collect data about novel cancer vaccines at the University of North Carolina, Chapel Hill, and support OpenAdmet, a group that runs competitions in which researchers try to predict drug effects. 

Teslo’s idea for a biotech archive received $500,000 and will be pursued by 1Day Sooner, an advocacy group representing clinical trial volunteers, which she advises.

“We expect many remaining breakthroughs in preventing and curing disease to come from pairing the intelligence of new models with more observations of the world—in other words, more data,” the OpenAI Foundation said in a statement.

OpenAI started as a nonprofit, but leader Sam Altman restructured it to form a for-profit corporation that develops new models, launches products, and is now planning an initial public offering of stock that could value it at $1 trillion.

Because the foundation holds a 26% equity stake in OpenAI, it is now be on track to become the richest charitable organization on the planet, potentially sitting on $250 billion in stock value. (By comparison, the Gates Foundation and a trust associated with it held about $180 billion at the end of 2025.)  

Making good use of that kind of money will not be easy. The foundation, based in San Francisco, is still hiring for many key roles and started ramping up its grantmaking only this year. Its largest single gift so far, of $100 million, was awarded in August to the Common Health Coalition, an organization that helps patients get access to drugs for hepatitis C.

OpenAI’s charitable efforts come even as apocalyptic fears have broken out about the possibility that runaway AI could wipe out all human life, possibly by launching a deadly bioweapon.

Those fears have been stoked by AI company insiders, some of whom say the chance of human extinction within the next decade is 10% or more. Last week, Altman and xAI founder Elon Musk both endorsed a call by Anthropic CEO Dario Amodei to “slow the pace at which we improve the capabilities of AI models” so that risk prevention can catch up.

Jacob Trefethen, an executive at the foundation, says it essentially operates separately from OpenAI but shares an official mission of ensuring that artificial intelligence “benefits all of humanity.”

“We’re starting grantmaking when we think the best way to achieve that mission is to make grants to external nonprofits, research institutions, and other third parties,” Trefethen said in an interview. He says the foundation hopes to give away $1 billion by the end of the year. 

The $500,000 grant to 1Day Sooner will help the group prove it can obtain the data troves of bankrupt companies, says the organization’s president and cofounder, Josh Morrison. He thinks nonexclusive copies of company datasets could be acquired for only “a few tens of thousands of dollars” each.

His organization is currently in possession of three datasets, two of them donated by Lumen Bioscience, a biotech that previously used the Chapter 11 strategy to gain insights into another company’s drug development efforts. 

Morrison says two other attempts to obtain drug company files this year proved unsuccessful, after 1Day Sooner’s bids were not accepted. 

Bankruptcies could become what some are calling a “new land grab” for AI training. Last month, Google won a bid to take over the corporate data of the failed carrier Spirit Airlines, including 100 million emails. That led to objections from flight attendants and others who worried that private or proprietary data could be exposed. 

The drug company files that 1Day Sooner is seeking are known as common technical documents. They typically contain the back-and-forth between companies and regulators, as well as detailed scientific and medical measurements, and essentially provide everything that is known about a drug.

According to Teslo, who is a writer for Works In Progress and a nonresident fellow at the Institute for Progress, a think tank in Washington, DC, a stockpile of such files could help turn an AI into a regulatory expert, which in her view could be one of the main ways AI helps speed cures to market.

“People say ‘We will invent AI, and AI will cure cancer,’ but that’s very removed from the messy reality and the regulatory process,” she says. “About 70% of the money and time in drug development is spent in clinical development—organizing the trials and testing the drug—but despite that, the process is basically a black box, especially for small biotech companies generating the innovations.” 

Exosomes are microscopic packages released by cells that carry proteins and other molecules throughout the body. The research team found that a shingles infection can cause nerve cells to release inflammatory signals and become highly active. When investigators exposed healthy nerve cells in the lab to exosomes collected from the blood of people with PHN, they found that the exosomes triggered in the nerve cells many of the same harmful changes seen during viral infection, even though no virus was present.

The findings suggest that PHN may develop because the body fails to fully turn off the healing response after shingles. Even after the virus has been cleared, exosomes continue delivering damaging messages that prevent nerves from recovering normally.

The study results indicate that chronic shingles pain may not simply be the result of damage caused during the initial infection, the study authors noted. Instead, biological signals carried by exosomes may continue to keep nerve cells in an irritated, dysfunctional state and prevent them from healing. The researchers describe this as a “failure-to-resolve” model, where the nervous system becomes stuck in a cycle of inflammation and abnormal nerve remodeling. This opens the door to entirely new approaches for predicting, preventing, and treating post-herpetic neuralgia.

The researchers, headed by Andrew Bubak, PhD, associate professor of neurology at CU Anschutz who studies the role of exosomes in infectious disease, reported their findings in Annals of Neurology, in a paper titled, “Circulating Exosomes Drive Persistent Neuronal Dysfunction in Post-Herpetic Neuralgia Patients,” concluding, “These findings establish a failure-to-resolve model in which persistent exosome-mediated signaling sustains maladaptive neuronal remodeling after viral clearance, identifying circulating exosome cargo as previously unreported mechanistic contributors to PHN pathogenesis and potential therapeutic targets.”

Varicella zoster virus can establish lifelong latency in sensory ganglia subsequent to primary infection and reactivate to cause herpes zoster—HZ; shingles—the authors explained. “Whereas most individuals recover from HZ, a substantial subset develop post-herpetic neuralgia (PHN), commonly defined as pain persisting for more than three months after rash …”. However, the mechanisms driving the change from acute viral injury to chronic neuropathic pain aren’t well understood. Bubak said, “We can completely stop the infection, yet in some patients the pain does not go away.”

The team’s prior work had demonstrated that plasma-derived exosomes from individuals with acute zoster infection, while non-infectious, carry prothrombotic and immunoregulatory cargo, and can activate platelets and induce proinflammatory cytokine production in vascular cells, promoting an inflammatory state.

Through their newly reported study the scientists discovered that nerve cells infected with the shingles virus in the laboratory became inflamed and showed signs of stress and irritation. Exposure to PHN patient-derived exosomes triggered inflammation in nerve cells and reduced the ability of nerves to grow and repair themselves. Exosome exposure also caused structural changes that may make nerves function abnormally and led to increased production of molecules associated with chronic pain. The exosomes didn’t kill the nerve cells and rather appeared to keep them in an unhealthy, dysfunctional state.

The researchers expected to see increases in the usual pain-signaling channels found on nerve cells. Instead, they found those channels were actually reduced. At the same time, levels of substance P, a chemical messenger involved in pain transmission, increased. This suggests that chronic shingles pain may be driven less by traditional nerve firing and more by ongoing chemical signals that keep the pain system activated. “Collectively, our findings point toward a potential ‘failure-to- resolve’ model in which PHN arises not from a fundamentally distinct biological process, but from the persistence and amplification of an initially adaptive, exosome-driven neuronal response,” the authors noted. Bubak said the findings could lead to new therapies to target these exosomes and relieve the pain.

Typical antiviral therapies such as acyclovir and valacyclovir target the replicating virus but do not consistently prevent PHN, “… reinforcing the notion that mechanisms independent of ongoing viral replication sustain the pathological state,” the team continued. “This is consistent with our findings, which suggest that non-infectious circulating exosomes, once generated during acute infection, persist and drive neuronal dysfunction independently of ongoing viral replication.”

At the same time, Bubak said, if the exosomes maintain this irritable state within the cell, they could also carry therapeutic agents to the target that block specific proteins and help nerves recover and regrow normally after shingles. “If exosome cargo contributes to the maintenance of the irritable nociceptor state, then circulating exosomes may represent both a source of therapeutic targets and a minimally invasive biomarker platform,” the authors also noted. “Early exosome profiles during acute HZ could potentially identify individuals at risk of developing PHN, enabling stratification and targeted intervention prior to the establishment of chronic symptoms.”

Bubak added: “This is an important discovery, one that offers hope to those who continue to struggle with often intense pain following infection with shingles.”

The post Exosomes Linked to Nerve Irritation, Dysfunction, and Lingering Pain After Shingles appeared first on GEN - Genetic Engineering and Biotechnology News.

FJBio is a global antibody discovery and engineering partner. Founded in 2012, the company works on taking programs from target to preclinical candidate within a single integrated workflow, run by one team across three centers of excellence: Porto (Portugal), Cambridge (U.K.), and San Diego (U.S.). The antibody company completed more than 1,400 programs for over 250 industry partners across pharma, biotech, and academia, with 20 partner assets in clinical trials.

The volume and complexity of experimental data generated across those programs made consistent, structured records a scientific and operational priority for FJBio, according to Sapio Sciences’ CCO Mike Hampton, who added that the company’s AI platform will serve as the informatics backbone across all of FJBio’s discovery and cell sciences operations.

Provides a single entity registry

Sapio’s ELN solution will record experimental data across phage display, screening, and cell sciences programs, replacing the need for scientists to capture data on paper templates before manually re-entering results into spreadsheets. As FJBio’s program portfolio has grown across three sites, the Sapio LIMS gives the company a single entity registry, from target registration through clone identification and screening results, searchable across programs, points out Hampton.

The solution is also designed to ensure integration of lab instruments, connecting instrument output directly to Sapio’s experiment records and eliminating manual data transcription at the bench. Structured client data reports, that were assembled by hand from individual experiment records will now come straight out of the platform, expected to return up to 40% of scientific staff time back to discovery, says a Sapio spokesperson.

“FairJourney Bio runs discovery programs of genuine depth and complexity across multiple international sites,” comments the spokesperson. “The Sapio Scientific AI platform gives their scientists a single, structured environment where experimental records connect directly to client deliverables and where time spent on data consolidation becomes time spent on science.”

“As our operations have grown across three international sites, we needed an informatics platform that could keep pace with that responsibility,” says Vidal. “The Sapio Platform gives our scientists a single connected environment for every experiment, every sample and every result, and it holds that data to the integrity and security standards our clients expect.”

Elain brings intelligence directly into FJBio’s scientific workflows, says Hampton. Working across the structured experimental data held within the Sapio Platform, Elain enables scientists to interact with their data using natural language, without leaving the environment where their experiments, samples and results are managed, he explains.

The post Consolidating Antibody Discovery Data with an AI Platform appeared first on GEN - Genetic Engineering and Biotechnology News.

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Emily Gaither

Engineer III, Downstream Purification
Thermo Fisher Scientific

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Panelist

Emily Gaither

Emily Gaither is a bioprocessing engineer specializing in downstream purification at Thermo Fisher Scientific. She has over five years of experience in downstream process development, with expertise in downstream process development, characterization, scale up and manufacturing implementation. Prior to joining Thermo Fisher Scientific in 2021, Emily worked at the University of Illinois Urbana-Champaign, where she supported bioengineering research and laboratory automation. Emily holds a bachelor’s degree in biology from North Central College.

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Bispecific antibodies can create purification challenges that conventional monoclonal antibody platform polishing is not always equipped to solve, with product-related variants “misbehaving” and closely resembling the desired heterodimer. Effective and efficient process development depends not only on identifying the appropriate selectivity from a toolbox of chromatography resins, but also how efficiently complementary unit operations interconnect for manufacturing.

In this GEN webinar, our expert speaker, Emily Gaither, will present a systematic path from high-throughput resin screening to the selection and sequencing of two polishing steps, using emicizumab, an asymmetric IgG4 bsAb as a case study. She will compare alternative process configurations and examine the purity, recovery, and process-performance tradeoffs used to identify a preferred downstream polishing train. Key takeaways from the webinar include:

• A systematic approach to screening polishing resins for bsAbs
• Strategies for matching resin selectivity to key impurities
• Insights into how polishing resin selection affects process performance
• Criteria for balancing purity, yield, loading, and robustness

A live Q&A session will follow the presentation, offering you a chance to pose questions to our expert panelist.

Produced with support from:

The post Right Resin, Right Order: A Two-Step Polishing Strategy for Bispecific Antibodies appeared first on GEN - Genetic Engineering and Biotechnology News.

Once an organ is removed from a donor’s body, the clock starts ticking. Surgeons usually flush the organ with a preservative solution, bag it, and put it on ice—where it immediately starts to degrade. The team has a matter of hours to get it into a recipient’s body.

There’s another option—one that has been growing in popularity in recent years, especially for donated organs that aren’t in the healthiest state. Some hospitals opt to put them on machines that pump them with nutrients and remove waste products, usually for around six to 12 hours. It’s a bit like being back in a body.

This allows doctors to assess the organs, and some recent studies suggest that time spent on these perfusion machines helps them do better once they’re transplanted. Now, scientists have found that perfused organs seem to get younger, at least at a molecular level.

The research, shared with MIT Technology Review, provides molecular clues as to why organs from younger donors are known to have a higher success rate. It might also help explain why perfused organs are less likely to fail once they make it into a recipient. 

The researchers behind the study hope to find new ways to test the health of donated organs and potentially develop additional tools to repair organs that might otherwise be discarded. “If [we] can improve the utilization of organs beyond what the current systems can do, then that’s a win in my book,” says Jesse Poganik, who studies aging at Brigham and Women’s Hospital in Boston and coauthored the study.

Clocking organs

Poganik—along with colleagues including Heidi Yeh and Alban Longchamp, transplant surgeons at Mass General Brigham—used “aging clocks” to assess donated livers. These are scientific tools designed to measure biological age—a result that is meant to convey more about the health status of an organ (or person) than chronological age.

In an initial experiment, the team used a clock to look at the patterns of chemical marks on DNA in 37 samples taken from 19 donated livers. Such epigenetic patterns are known to change as we age. But when the team compared samples from livers kept on ice and those that were perfused, the team found a “striking” pattern in the latter.

“Machine-perfused livers, in spite of being older or having other disadvantageous characteristics, had a biological age that was lower than [non-perfused] livers that were chronologically younger,” says Yeh, who led the work.

To investigate further, Yeh and her colleagues analyzed another 208 samples from 103 donated livers. This time, they used different aging clocks—ones that essentially measure how genes are working. They studied samples biopsied from the livers after they had been stored for up to around six hours either in cold storage or on machine perfusion.

In most cases, they also assessed a second sample taken around an hour after the livers had been transplanted into a recipient. Once the organ’s blood supply is reestablished in the body, “you have a few other things to do,” says Longchamp. “Then you just do a quick biopsy before you close.”

According to the clocks, which were developed to measure age and risk of death, the machine-perfused livers were biologically younger, the team found. “Pumping them at 34 degrees with oxygen and nutrients actually reversed the biological age,” says Longchamp. The results have been been shared with colleagues at an industry conference, he says. 

“If you adjust out chronological age … to have a fair head-to-head comparison, the difference between the two is on the order of 30%,” says Poganik. “It’s logical to say that perfusion drives this effect.”

The biological ages of all the livers tended to increase as soon as they were put into a recipient’s body, probably as a result of stresses on the organs. But still, the effect endured—the perfused organs remained biologically younger. 

Nathanael Raschzok, a transplant surgeon at Charité Universitätsmedizin Berlin in Germany who was not involved in the research, says the work is impressive. But it’s not yet clear what these changes might mean for the recipients of these organs, he says. The organs in the study were donated by people in their 30s, 40s, and 50s. Raschzok wants to know the effect of perfusion on the liver of an 80-year-old. “Every so often, we use organs from 70-, 80-, 85-year-old donors,” he says.

A better understanding of why the organs appear to be getting biologically younger might lead to therapies that achieve the same effect with a drug that could potentially be used to treat a donated organ for a fraction of the price, he adds. That’s important because perfusion is expensive—Raschzok says it costs around €10,000 in Germany (a quarter of the budget for a transplant), while the cost in the US comes to around $80,000 to $100,000 per organ, says Yeh.

Molecular repair

Yeh and her colleagues weren’t able to study most of the livers before perfusion. That’s because donated organs are generally not considered to be under the purview of the hospital until they’ve been placed on perfusion machines, she says. (Organ procurement procedures vary, but for the team as Mass General Brigham, donated organs are put on perfusion devices at the donor’s hospital. “There’s this sort of nebulous period where it’s not clear who the organ belongs to,” says Yeh.)

Still, by looking at the genes and molecular pathways that seem to be altered in perfused organs, she and her colleagues can garner some clues. At a molecular level, the team saw changes in cell pathways linked to inflammation and the structure of tissues, for example. They also saw more activity in a pathway that allows cells to remove and recycle damaged cell parts, says Yeh.

Poganik hopes to develop some kind of test that would determine which organs, on the basis of their biological age, are suitable for transplantation. He and his colleagues are also experimenting with potential drug treatments that might push the biological age of an organ even lower.

In the meantime, any liver that is not from a “perfect, young, brain-dead donor” could probably benefit from perfusion, says Yeh. The devices are already transforming transplant surgery. Just a few years ago, she says, she and her colleagues would avoid using livers from people who’d suffered a circulatory death (when the heart stops beating and there’s a damaging lack of blood flow to organs) and were over 40. Today, they use livers from such donors over the age of 70. “Perfusion has completely changed the landscape of transplantation in the last three years,” she says.

“People with this genetic variant have dramatically hastened onset of disease, but we didn’t know why,” said Michael Hayden, MBChB, PhD, professor at the Centre for Molecular Medicine and Therapeutics at UBC. “This work answers that question and provides dramatic evidence that repeated expansion of the mutation is an important driver of Huntington disease and a potential treatment target.” Hayden is senior author of the researchers’ published paper in Neuron, titled “Loss of interruption in the HTT CAG repeat is associated with increased somatic expansion and loss of medium spiny neurons in HD.”

Huntington disease is a rare, inherited neurological disorder that causes the progressive breakdown of nerve cells in the brain. The condition affects movement, thinking and emotional well-being, and there is currently no cure or treatment to slow progression.

One way to think about the process is like a typo in a document that keeps getting copied. With every copy, the mistake is replicated and interferes with the message. “HD is caused by 36 or more uninterrupted CAG repeats in exon 1 of the Huntingtin gene (HTT), and the number of inherited CAG repeats is the primary determinant of the age at which symptoms first emerge,” the authors explained.

In Huntington disease the mutation continues to repeat and expand within neurons over time. As those repeats become longer, they interfere with normal cell function and make brain cells increasingly vulnerable to damage and death. “Medium spiny neurons (MSNs) are gradually lost in HD and undergo selective somatic CAG expansion, but it is unclear how somatic expansion relates to MSN pathology,” they continued.

Hayden added, “When we looked at the neurons that are dying in Huntington disease, we saw much greater expansion of the genetic mutation. This continues to strengthen the argument that DNA expansion is an important cause of disease.”

A small proportion of people with HD have a particular genetic variant, and researchers have known for years that these individuals develop Huntington disease earlier in life. “CAG and CCG loss-of-interruption (CAG-CCG LOI) variant hastens the onset of HD motor symptoms by up to 12.5 years and accelerates clinical measures of disease progression when compared with patients with the canonical sequence,” the team noted.

But it wasn’t known why this seemingly small change in DNA had such a dramatic effect on disease onset and progression. People carrying the variant had dramatically larger expansions of the Huntington mutation inside their neurons, occurring about five times more frequently than in patients without the variant. They also had fewer surviving neurons and earlier loss of particularly vulnerable nerve cells.

For their reported study the researchers analyzed blood samples and post-mortem brain tissue. “Here, we apply complementary approaches to assess somatic HTT CAG expansion from peripheral blood, postmortem brain tissues, and isolated MSNs of HD patients with and without the CAG-CCG LOI modifier variant and quantify MSN loss in the CAG-CCG LOI donor caudate.” They found a clue that helps explain one of the mysteries of Huntington disease, which is why a mutation that is present in every cell of the body primarily damages the brain.

Although the mutation exists throughout the body, the researchers found that the expansion process appears to be highly concentrated in certain cells of the brain. Blood samples, by contrast, showed little evidence of the dramatic changes that take place within the brain’s neurons. “Our interrogations of somatic expansion in blood, brain, and striatal MSNs of donors with and without the CAG-CCG LOI show this modifier does not increase small expansions in blood or bulk brain tissues, yet profoundly increases the proportion of genomic large (111–150) and very large (>150) CAG expansions in affected striatal MSNs,” they wrote.

“The mutational expansion seems to be selective for the brain,” Hayden added. “That may help explain why Huntington disease, even though the mutation is in every cell, is fundamentally a brain disease.”

The findings suggest blood tests are not a reliable indicator of the disease unfolding inside the brain, which is an important consideration for future Huntington disease research and clinical trials. “Peripheral blood DNA does not capture increased somatic expansion in MSNs, suggesting that blood DNA is a poor biomarker for disease-relevant somatic expansion in HD-affected neurons,” they noted.

While other factors besides expansion likely contribute to neuron loss, the findings provide some of the strongest human evidence to date that expansion of the Huntington mutation is a key factor in disease progression. “It validates repeat expansion of the DNA as an important therapeutic target in Huntington disease,” Hayden said. “If we can suppress that expansion, it may be possible to delay progression or delay the onset of disease.” And as the authors further commented, “Our study further underscores the need for cell-type-specific studies across other repeat expansion disorders that preferentially affect specific neuron populations.”

Several experimental therapies in development aim to slow or prevent this mutation growth before the damage occurs. While more research is needed, this study’s findings show research is moving in the right direction for a disease which has been so difficult to treat.

The post Why Does a Particular Genetic Variant Lead to Accelerated Huntington Disease Development? appeared first on GEN - Genetic Engineering and Biotechnology News.

There are currently over 100 different serotypes of S. pneumoniae. While it is known that different subtypes of S. pneumoniae can lead to varying infection rates in different populations, important gaps remain in our collective understanding of how things such as humidity, temperature, and air pollution impact the timing of disease, and how risks vary by individual age and bacterial subtype.

Now, researchers suggest that the subtype of S. pneumoniae, together with air pollution exposure, impacts the rate and timing of invasive disease—with some strains linked to immediate infection after air pollution exposure, and others taking several weeks. The findings also suggest that older adults and young children are more vulnerable during periods of high air pollution, and that improving air quality could lower disease risk. Understanding what type of bacterial strains are circulating, and how environmental factors shape infection rates, could inform future public health policies, protect those most at risk, and prepare hospitals for outbreaks.

The work is published in Nature Microbiology in the paper, “Pneumococcal population structure influences the effects of air pollution on invasive disease risk in South Africa.”

“While we found that temperature and air pollution generally increase the risk of invasive pneumococcal diseases, such as bacterial meningitis, our research also suggests that it is the bacterial subtypes a person is carrying that modulate infection rates,” notes Sophie Belman, PhD, previously at the Wellcome Sanger Institute and Barcelona Supercomputing Center, and currently an assistant professor at Yale School of Public Health. “The strain of bacteria impacts the timing of disease and who might be more at risk depending on their respiratory microbiome, meaning that the risk is not the same in every situation or for every person. By extending our findings to other parts of the globe, we will better understand who has the highest health risk from environmental exposures, and what factors need to be addressed in different regions, such as improving air quality in cities.”

This new study examined roughly 59,000 cases of IPD across 19 years from South Africa’s national GERMS-SA surveillance program. In South Africa, between 40-60 per cent of children carry S. pneumoniae. The researchers found that different subtypes of S. pneumoniae responded differently to higher air pollution exposure, noting three subtypes (14, 19A, and 8) were linked to the greatest risk of IPD following exposure.

Additionally, they found that different subtypes were linked to differences in the timing of disease risk. While the highest risk of IPD peaked roughly two weeks after air pollution exposure, in areas where subtypes 4, 8, 23F, and 19F were common, there was an immediate increase in disease risk, occurring within the same week.

The team accounted for other factors including temperature, humidity, and population density to ensure that the effects were measured as accurately as possible. They also noted that high temperatures were associated with an immediate increase in disease risk, and cold temperatures led to a delayed rise in cases. The team suggests that cold weather slows bacterial transmission or that damage from seasonal viruses could make it easier for bacterial infections to follow.

The authors suggest that integrating environmental monitoring with genomic surveillance of S. pneumoniae could help predict infection spikes, inform vaccination strategies, and support healthcare providers prepare during periods of poor air quality. The study also provides further evidence that reducing air pollution may yield important benefits for infectious disease prevention, particularly in areas with high levels of exposure, such as cities.

The post Pneumococcal Subtypes Influence the Impact of Air Pollution on Disease Risk appeared first on GEN - Genetic Engineering and Biotechnology News.

The investment will add downstream fermentation technology to the site, increasing capacity for the development and manufacture of complex pharmaceutical intermediate. Creating approximately 50 new jobs, the expansion will further reinforce the Fermas site as one of Evonik’s key biotechnology hubs, said Lauren Kjeldsen, member of the management board and COO at custom solutions, Evonik.

“Today is an important step in our strategy to expand our biotechnology platform and support our customers with innovative, scalable, and sustainable manufacturing solutions,” continued Kjeldsen. “Biotechnology demonstrates how economic growth and sustainability can go hand in hand.”

Compared with conventional chemical synthesis, fermentation-based processes can offer a more sustainable route to selected intermediates by reducing the need for organic solvents and minimizing process-related waste. The Fermas site already operates on 100 percent green electricity and uses renewable and certified raw materials in selected production processes.

“This investment demonstrates the company’s confidence in biotechnology and in Slovakia as a location where innovation turns into industrial scale products,” added Miroslav Havlik, general manager of Evonik Fermas.

Evonik Fermas, which was founded in 1992, has evolved from amino acid production into a biotechnology manufacturing hub serving the pharmaceutical, personal care, nutrition, and specialty chemical industries. In recent years, the site has also become a major location for Evonik’s biotechnology activities, including the launch of an industrial-scale rhamnolipid biosurfactant production facility.

The post Evonik Expands in Slovakia appeared first on GEN - Genetic Engineering and Biotechnology News.

What does seem certain is that pharmaceutical tariffs will reduce the funds biotechnology firms have to develop treatments, discourage investors, and threaten patients’ access to drugs. For these reasons, pharmaceuticals have traditionally been considered off-limits for tariffs.

“At a time when the U.S. is competing to maintain global leadership in biotechnology, policies that raise costs, discourage innovation, and weaken our competitive position ultimately make it harder to deliver for patients and strengthen the economy,” warns Kelly Seagraves, VP of National Security & International Affairs at the Biotechnology Innovation Organization (BIO). “We urge the Administration to consider alternative policies for bolstering U.S. manufacturing and resilient supply chains.”

For now, BIO continuously seeks guidance on tariff compliance and potential exemptions, to inform the industry.

On Sept. 14, with two weeks until implementation, BIO’s experts say much of the necessary federal guidance is still missing, and the lack of information adds further challenges to an already challenging situation.

What is known

Based on a Presidential Proclamation signed April 2, 100% ad valorem tariffs on patented pharmaceutical products and associated input materials go fully into effect on Sept. 29.

There are several potential reductions or exemptions for specific companies, countries, and products:

•  Countries of origin matter: The tariff is reduced to 15% for non-exempt products from Japan, the EU, Korea, and Switzerland/Liechtenstein. Tariffs on U.K. imports are 0% following an August 4 Federal Register Notice from the Department of Commerce.
• Companies can reduce tariffs to 20% or 0%, by negotiating an onshoring plan with the Department of Commerce or by negotiating both an onshoring plan and a Most Favored Nation (MFN) pricing agreement with the Department of Health and Human Services. These reductions are temporary, expiring April 2, 2030 and January 20, 2029, respectively.
• Products that are exempt include generics and biosimilars until April 2, 2027, with a mandate to reconsider generic eligibility in 2027. The Proclamation also notes several classes of drugs that may be exempt, but only if they originate from a country with a trade and security framework agreement or they meet an urgent U.S. health need.

What is unknown

The lack of specific guidance for the industry on what products will be exempted and how exemptions will be granted means both industry and the U.S. government will be under immense time pressure, making it highly unlikely the pharmaceutical tariff regime can be fully implemented on Sept. 29. Implementation will require further guidance, including:

• Specifics on product exemptions: Companies need to know whether their products qualify for Clause (3)(d) exemptions. These may include orphan drugs, nuclear medicines, plasma-derived therapies, fertility treatments, cell and gene therapies, antibody drug conjugates, and medical countermeasures for public health threats. However, there is uncertainty about the details of qualifying for these exemptions. Other questions concern importing branded, off-patent drugs, or the input materials to manufacture in the U.S. patented pre-commercial products that are not yet making money.
• Case-by-case product decisions for an “urgent U.S. health need”: The Commerce Department has indicated decisions about exemptions for meeting an “urgent U.S. heath need” will be made on a case-by-case basis. Yet companies are still awaiting Commerce guidance on the process to request an exemption.
• Preparing the requested information undoubtedly increases compliance and administration costs—a particular challenge for smaller and mid-size biotech companies with small teams and limited capital. Further, application and government review could be time-consuming, adding to uncertainty about when tariffs apply and how much they will be.
• Countries with trade and security framework agreements: The second avenue for a Clause 3(d) exemption is that the product originates from a specific set of countries. The U.S. government has still not shared which countries these are. 
• MFNs and onshoring: There are no clear parameters for MFN or onshoring deals, which are apparently handled case-by-case.

This continued uncertainty raises questions about short-term implementation. In one scenario, all eligible pharmaceutical products would be charged tariffs based on country of origin, and companies granted exemptions might receive refunds later. Alternatively, the government could delay collection of tariffs on potentially exempt products but collect retroactively. A final option would be a Presidential decision to forego or delay implementation, giving both companies and the government sufficient time to determine eligibility for exemptions.

Impacts on biopharma and patients

Impacts are hard to predict with so many unknowns about the total amount of tariffs that will be collected and what companies and products will be charged, BIO experts say.

For many companies, an exemption could be the difference between 100% tariff rates and no tariffs. The resulting uncertainty around costs for the industry and individual companies is an impact itself. It frightens investors and complicates business planning, making companies hesitant to spend on R&D when their capital needs are uncertain.

The challenge is particularly acute for the small- to medium-sized companies that are responsible for 71% of the industry’s output and 54% of the new drug applications, according to BIO. The smaller innovative companies generally have less available capital to adjust to shocks like tariffs.

The anticipated impact on patients will be two-fold. First, out-of-pocket costs can be expected to rise when importing drugs is 100% more expensive. Second, there will be negative impacts on innovation as companies that lose income due to tariffs spend less on R&D. Access challenges may arise if some companies stop importing certain drugs into the U.S. altogether.

What to do instead of tariffs

The tariffs are being implemented after a Department of Commerce Section 232 investigation determined that global supply chains are risky, and that onshoring drug production bolsters national security. But BIO experts note that tariffs actually create new disturbances in the existing supply chain.

There are better ways to protect global supply and attract manufacturing back to the U.S., according to BIO. These include strategic incentives, such as tax credits for building domestic manufacturing, and investments in U.S. biotechnology and biomanufacturing workforce development.

Appropriately targeted, non-tariff measures could secure supply chains while freeing small- and medium-sized biotechs to invest more in innovation. The improved clarity and certainty would benefit biotechs, investors, and patients.

The post With pharmaceutical tariffs looming, guidance on compliance is still lacking appeared first on Bio.News.

Arguably the most dramatic loss faced by Novartis is satisfaction with its direction by major investors—one of which, Artisan Partners, went public with criticism of the company’s board.

M. David Samra, managing director at Artisan Partners and founding partner of International Value Group, called on the board—specifically, its chairman Giovanni Caforio—to strengthen its oversight of the company’s acquisitions.

“I think he needs to make changes at the board level. One of them should be on improving the team that’s doing ​these deals because clearly they have been uninspiring at best,” Samra told Reuters in an interview.

“The party is over,” Samra declared, complaining that the acquisition deals lowered the value of Novartis shares. “The acquisition track record is not very good.”

Among the acquisitions cited by Samra were Novartis’ $12 billion buyout of Avidity Partners, a deal completed in February with the aim of bolstering the buyer’s neuroscience pipeline with three late-stage programs—del-desiran and two other candidates in a new class of RNA therapeutics that Avidity and now Novartis call Antibody Oligonucleotide Conjugates (AOCs).

The companies have reasoned that the AOC approach can safely and effectively treat serious genetic neuromuscular disorders by delivering RNA to muscle tissue via TfR1 mAb, in order to enable modulation of the genetic mechanism of disease.

But that argument was undermined when Novartis acknowledged that del-desiran failed the pivotal trial (HARBOR, NCT06411288) by missing the study’s primary endpoint of statistically significant improvement vs. placebo in video Hand Opening Time (vHOT) through week 54. vHOT is a frequently used measure of hand myotonia, according to a 2024 study, and involves clinical experts reviewing videos to measure the time from hand grip to opening.

Del-desiran is an AOC candidate designed to target the underlying cause of DM1. The therapy consists of a muscle-targeting monoclonal antibody that binds to the transferrin receptor 1 (TfR1) and is conjugated to a small interfering RNA (siRNA) designed to induce degradation of the disease-causing toxic myotonic dystrophy protein kinase (DMPK) mRNA.

Del-desiran has received the FDA’s Orphan Drug, Fast Track, and Breakthrough Therapy designations, as well as the European Medicines Agency’s Orphan Medicinal Product Designation.

“Needs to be penalized”

“If you do a $12 billion deal and it goes to zero, the management needs to be penalized for that,” Samra said, though he acknowledged that the Avidity acquisition may yet yield successful candidates that can be developed into marketable drugs.

Samra also took issue with Novartis’ acquisition of MorphoSys for €2.7 billion ($3.1 billion), completed in May 2024. That deal was intended to bolster the buyer’s oncology pipeline with what seemed like a promising late-stage myelofibrosis candidate in pelabresib, as well as an early-stage candidate under study in patients with solid tumors or lymphomas.

Within months, Novartis delayed earlier plans to pursue mid-2024 approval filings for pelabresib and later said more time was needed to decide a regulatory path for the drug based on 48-week data from the Phase III MANIFEST-2 trial (NCT04603495). However, the combination of pelabresib plus ruxolitinib met the study’s primary endpoint, a reduction of at least 35% in spleen volume from baseline (SVR35) at 24 weeks: 65.9% of pelabresib-ruxolitinib patients (N=214) vs. 35.2% of placebo-ruxolitinib patients (N=216)

Earlier this year, Novartis launched the Phase III MANIFEST-3 trial (NCT07357727) assessing pelabresib in combination with ruxolitinib in patients with myelofibrosis. Novartis markets ruxolitinib outside the United States as Jakavi®, while Incyte markets the drug Stateside as Jakafi®. The trial’s estimated completion date is May 2028.

Del-desiran was one of three clinical setbacks for Novartis within a week. On September 4, the company and partner Ionis Pharmaceuticals (Nasdaq: IONS) acknowledged that their co-developed pelacarsen failed the Phase III Lp(a)HORIZON trial (NCT04023552) by missing its primary endpoint of reducing the risk, compared with placebo, of cardiovascular events.

Two days earlier, Novartis paused eight trials assessing its autoimmune and neurological disease candidate rapcabtagene autoleucel (rap-cel), after three patients treated with the personalized, CD19-directed chimeric antigen receptor T cell (CAR T) therapy died after experiencing immune effector cell-associated hemophagocytic syndrome.

Not Blaming CEO

Samra stopped short of blaming Vas Narasimhan, who has been Novartis’ CEO since 2018, for the company’s clinical setbacks, saying the chief did a “very good job”—with Reuters suggesting by juxtaposition a possible explanation: The company’s shares have jumped 60% in value during his tenure at the helm.

But Novartis’ primary shares in Switzerland have only risen 2% from CHF 108.50 ($132.88) so far this year and climbed 11% from CHF 101.78 ($124.65) year-over-year.

Worse, the announced failure of del-desiran on September 8 propelled Novartis shares to their worst one-day selloff since March 2020, early in the COVID-19 pandemic. Shares trading on the SIX Swiss Exchange skidded 11% from CHF 125.46 ($153.64) to CHF 111.80 ($136.91), while Novartis’ American depositary shares traded on the New York Stock Exchange slid 14% from $159.99 to $137.72.

Both shares all but plateaued for the rest of the week, failing to regain momentum. At the end of trading Friday, the SIX Swiss shares inched up 0.2% to CHF 112.04 ($137.21), while the NYSE shares dipped a further 0.4%, finishing the week at $137.16.

Artisan’s flagship fund, the Artisan International Value Fund, listed Novartis as fourth among its top 10 holdings, accounting for 3.6% of its total portfolio as of June 30, according to its most recent quarterly fact sheet. As of that date, Artisan reported $45.184 billion in assets, which would have made the value of Artisan’s stake in Novartis approximately $1.627 billion.

That stake likely increased later in the summer before the del-desiran news, since Artisan’s website lists the total value of the value fund at $46.001 billion as of August 31.

In addition to del-desiran, Novartis acquired delpacibart zotadirsen (del-zota), an Exon 44-targeting AOC designed to treat Duchenne muscular dystrophy (DMD), and delpacibart braxlosiran (del-brax), an AOC intended to treat facioscapulohumeral muscular dystrophy (FSHD) by targeting DUX4.

Del-zota is under evaluation in the Phase II EXPLORE44OLE (NCT06244082) trial following completion in November 2024 of the Phase I/II EXPLORE44 (NCT05670730) study. Del-brax is being assessed in the Phase III FORTITUDE-3 trial (NCT07038200).

In June, Novartis trumpeted positive data from the FORTITUDE Phase I/II trial (NCT05747924) of del-brax, saying the study’s biomarker cohort met its primary and key secondary endpoints, with reductions in KHDC1L (cDUX) and creatine kinase biomarker levels indicating both strong target engagement and reduction in muscle damage in patients with FSHD.

Investors weigh in

Samra’s criticism of Novartis’ board was echoed by what Reuters said was some of seven other representatives of shareholders, five of whom were quoted by name in a follow-up article.

“It’s ​going to take a while for confidence to return,” said Gillian Hollenstein, lead manager at Point Capital Navigator Fund, which, as of September 10, listed Novartis as tenth of its top 10 holdings, accounting for 1.8% of its total portfolio. The fund reported CHF 124.38 million ($152.33 million) in total assets as of that date, making Point Capital’s stake total CHF 2,238,840 (more than $2.7 million).

“They ​would have been better off doing some more smaller acquisitions, bolt-on ones rather than trying to hit it out of the park,” Hollenstein added.

Avidity was the largest of 11 biopharma acquisitions Novartis has carried out since 2023. They all could total up to $32.9 billion if Novartis achieves the milestones called for in five of the deals.

“It’s a little bit premature to call for heads at this point,” said Daniel Bolanowski, portfolio manager at investor Arctic Asset Management, since Avidity-created del-zota and del-brax could ultimately succeed in the clinic and generate revenue. But Bolanowski added that the stock selloff suggested “a deeper trust issue” with the company’s business development approach, beyond the failure or reduced value of del-desiran.

Arctic Aurora, as of June 30, had a Novartis investment it quantified as 2,660 shares valued at a total NOK 4,124,818 ($443,994.25), accounting for 1.23% of its portfolio.

Michael Hannig, a buy-side analyst covering global healthcare and portfolio manager of a DACH [Germany, Austria, and Switzerland] small- and mid-cap fund at DJE Kapital, suggested to Reuters that Novartis could regain investor confidence and replenish its pipeline following patent cliff exclusivity expirations by pursuing deals in the $5 billion to $10 billion range for late-stage assets or ​drugs nearing approval, subject to due diligence: “Larger transactions will likely be assessed carefully by ‌investors considering ⁠the mixed market reception to several prior deals.”

DJE Kapital has disclosed having more than €18.9 billion ($21.9 billion) in total assets under management across its funds as of  but does not disclose the portfolio details of its individual funds.

Executives at two other Novartis investors, Bellevue Asset Management and Union Investment, defended Novartis: Guy Bettschart-Ghassabi, healthcare analyst at Bellevue Asset Management, noted that the HARBOR study was designed by Avidity before its acquisition by Novartis, while Markus Manns, portfolio manager at Union Investment, said the failure of del-desiran and pelacarsen was unfortunate but within normal probabilities of drug development success.

“They have to work harder to fulfill their post-2030 goals,” Manns said, “but it’s in the same camp as most other pharma companies.”

Bellevue Asset Management finished last year with AUM of CHF 5.3 billion (nearly $6.5 billion) while Union Investment reported €534.6 billion (about $620.3 billion), according to public disclosures that also exclude portfolio details.

Good news for competitors

Myles R. Minter, PhD, a partner and biotechnology analyst with William Blair, wrote in a research note that Novartis’ clinical miss for del-desiran is a positive development for several potential competitors, which, like the Swiss pharma giant, are also developing drugs designed to treat DM1 by targeting DMPK. These include:

• Dyne Therapeutics (Nasdaq: DYN), which is developing zeleciment basivarsen (z-basivarsen or DYNE-101), an anti-TfR1 FAb-conjugated antisense oligonucleotide (ASO). Z-basivarsen is under study in the Phase III HARMONIA trial (NCT07486934), after generating positive strength and cognition data in March from the Phase I/II ACHIEVE trial (NCT05481879), set to read out new one-year data later this month. Topline data is expected from ACHIEVE’s registrational expansion cohort in the first quarter of 2027.
• Sarepta Therapeutics (Nasdaq: SRPT) and Arrowhead Pharmaceuticals (Nasdaq: ARWR), which are co-developing SRP-1003 (formerly ARO-DM1), an RNA interference (RNAi) conjugate being assessed in a Phase I/IIa trial (NCT06138743) that generated positive early clinical results and is set to read out multiple ascending dose data later in the second half. Sarepta is in-licensing SRP-1003 from Arrowhead under a collaboration announced in 2024 that generated for Arrowhead $825 million in upfront cash and equity and could generate an eye-popping $10 billion in milestone payments.
• PepGen (Nasdaq: PEPG), which is developing PGN-EDODM1, which uses the company’s enhanced delivery oligonucleotide (EDO) technology to deliver a therapeutic oligonucleotide designed to restore the normal splicing function of MBNL1, a key RNA splicing protein. PGN-EDODM1 is under study in the Phase II FREEDOM2 trial, where PepGen has fully enrolled the 10 mg/kg MAD cohort, data from which are expected to be reported in November. In August, the trial’s independent data and safety monitoring board (DSMB) approved advancing to the highest dosage cohort of 12.5mg/kg.
• Vertex Pharmaceuticals (Nasdaq: VRTX) and Entrada Therapeutics (Nasdaq: TRDA), which are co-developing VX-670, which is expected to read out data from the Phase I/II GALILEO trial (NCT06185764) later in the second half of this year. VX-670 is a phosphorodiamidate morpholino oligonucleotide (PMO) connected to a cyclic peptide containing motif that Vertex in-licenses from Entrada under an up-to-$735 million collaboration announced in 2022.

“Today’s miss from del-desiran leaves open space to fill within the DM1 patient class, and we view Vertex/Entrada’s VX-670 as compelling,” Minter wrote, based on its endosomal escape vehicle (EEV) platform: “We view Entrada’s muscle-targeted EEV as possessing an impressive safety profile to date, which we view as important for entrance into higher dosing regimes that may be required for sufficient muscle tissue penetration and vHOT improvements to translate into a registrational trial setting.”

Lower projected sales

Novartis’ disappointing outcome for del-desiran in the HARBOR trial compelled analysts to cut their sales forecasts for the candidate, which Narasimhan projected had “$5 billion-plus peak sales potential” in an interview with Bloomberg TV.

Stefan Schneider, PhD, senior equity analyst, pharma with Vontobel Asset Management, removed the firm’s previous peak annual sales projection of $3 billion for del-desiran from its valuation model and cut its Novartis price target from CHF 128 ($156.77) to CHF 125 ($153.09). Vontobel previously gave Novartis a 50% probability of success for del-desiran.

Michael Schmidt, PhD, a senior biotech analyst and senior managing director at Guggenheim, slashed the firm’s risk-adjusted 2033 sales forecast for del-desiran by 45% from $1.76 billion to $960 million, with a 60% probability of success. The firm previously identified del-desiran and pelecarsen as critical to Novartis’ success from 2030 onward, along with a third candidate that recently succeeded in the clinic—remibrutinib, which generated positive topline data in the Phase III REMODEL-1 (NCT05147220) and REMODEL-2 (NCT05156281) in relapsing multiple sclerosis, Novartis said.

Remibrutinib is now marketed by the company as Rhapsido® in chronic spontaneous urticaria (CSU) in adults who remain symptomatic despite H1 antihistamine treatment.

Novartis has maintained its guidance to investors, foreseeing net sales growth at a compound annual rate of 5% to 6% at constant currencies between 2025 and 2030.

The post StockWatch: Novartis Loses More than Market Value After Phase III Failure appeared first on GEN - Genetic Engineering and Biotechnology News.

The work was done by scientists from Georgia Tech and Vanderbilt University. The human lymphoid organoid was developed by a team led by Ankur Singh, PhD, a professor of bioengineering and director of the Center for Immunoengineering at Georgia Tech. They developed it by isolating B cells from human tonsil tissue and blood sources and growing them in an environment similar to lymphoid tissue. They used inactivated influenza virus to overcome challenges associated with culturing B cells and getting to transform into antibody secreting plasma cells. 

Meanwhile, scientists in the lab of Krishnendu Roy, PhD, dean of engineering and professor of biomedical engineering at Vanderbilt University, designed a microfluidics-based vascularized microenvironment for the bone marrow chip that mimics the conditions found in human bone marrow. Essentially, they tried to “mimic the structure, fundamental biological functions, and spatial microenvironments” of human bone marrow in order “to ask questions about human organ-like behavior in this more simplified model,” Roy explained. 

As explained by the developers, the final model is assembled within a three-by-five stack of 96-well plastic plates, that are each less than half-an-inch thick. It features multiple channels that are coated with a gel-like material similar to bone marrow with nutrients and growth factors to support plasma cell function and maintenance.  Its layers correspond to an area at the outer edge of the bone marrow cavity, known as the endosteal subniche, where plasma cells are stored. The model also replicates an area deeper inside the center of the bone marrow, the perivascular subniche, which surrounds a network of blood vessels, where plasma cells proliferate and are activated.

“It is nearly impossible to achieve high imaging resolution of plasma cells in living human bone marrow,” Singh said. Though it is possible to “do some level of imaging in the bone marrow of a mouse” which is where some previous efforts have been focused. 

Now with this new model, scientists will be able to run new types of experiments. “A fundamental question [that] our study addresses [is] why it is that when B cells are ready to make antibodies, they relocate from lymph nodes, the spleen, and other organs and enter and take up residence in bone marrow,” Singh said. “Another is a question of the role that the environment of bone marrow plays in orienting those cells and responses to reinfection.”

Furthermore, the model can be seeded with cells from unique patient populations to study things like the effects of aging on plasma cell function. It could also be used to study cells from people with autoimmune or allergic diseases to understand how autoimmunity or allergy-promoting plasma cells are produced and maintained. Other studies could focus on addressing questions such as why B cells show a stop-and-go pattern of movement and whether it is part of a migration pattern in the bone marrow. 

The post Bone Marrow-on-a-Chip Model Offers New Window Into Immune Cell Development and Behavior appeared first on GEN - Genetic Engineering and Biotechnology News.

Transcenta will receive an upfront payment of $1.5 million and will be eligible for milestone payments upon the achievement of specified conditions. Through this collaboration, WuXi Biologics will become Transcenta’s strategic partner for CMC development and supporting molecules across Transcenta’s development pipeline.

A Transcenta spokesperson explained that the HiCB platform integrates intensified continuous perfusion upstream processing with hybrid continuous downstream purification, enabling a step-change in productivity, achieving an increase in productivity compared with conventional fed-batch processes.

HiCB can significantly reduce cost of goods, lower capital investment, and enable agile production, claims the company official, while providing a solution for improving recovering yield and product quality for complex biologics.

Transcenta, headquartered in Suzhou, China, is a clinical-stage biopharmaceutical company with expertise in biologics discovery, translational research, clinical, and process development. The company develops a pipeline of over ten therapeutic antibody candidates spanning oncology, bone, and kidney disorders.

The post Transcenta Therapeutics and WuXi Biologics Team Up to Accelerate Commercialization of HiCB Technology appeared first on GEN - Genetic Engineering and Biotechnology News.

However, a long-standing challenge in neuroscience and neuropathology has been how to continuously observe biological processes that unfold over hours, days, and even weeks in the brain.

Now, researchers at Johns Hopkins Medicine have demonstrated a new approach to brain imaging that enables continuous monitoring of brain activity and the physiologic changes associated with neurological disease progression for more than 24 hours in freely moving mouse models. The cloud-based miniaturized microscope, CloudScope, operates autonomously and allows scientists to access live imaging data remotely from anywhere in the world, creating new opportunities to study diseases as they develop over time.

The study demonstrates the ability to remotely capture and analyze changes in brain activity, blood flow, blood vessel remodeling, oxygenation and cellular behavior over extended periods, providing a more holistic picture of brain disease progression than conventional imaging approaches.

This work is published in Nature Methods in the paper, “A cloud-based miniscope for neurosurveillance of brain health and disease in freely behaving animals.”

“We started with a fundamental question: If we wanted to image a seizure or brain tumor formation continuously in a preclinical or animal model over 24 hours or longer, how would we do that?” says Arvind Pathak, PhD, professor of radiology, oncology, and biomedical and electrical engineering at Johns Hopkins. “The consequence of us working through this question and its associated challenges is what resulted in this innovation.”

Using this approach, the team captured spontaneous seizures occurring several hours after a drug-induced seizure in mice, events that would have been missed using conventional short-term imaging methods. In separate studies of brain cancer, researchers were able to characterize the behavior of individual cancer cells and observe dynamic changes in the brain’s microenvironment as the disease progressed. These findings suggest that continuous monitoring may reveal critical biological events that occur outside the limited observation windows typically used in laboratory research.

“Most central nervous system diseases develop over hours, days or even weeks. Yet modern imaging tools are designed to continuously probe only a small fraction of this time window,” says Janaka Senarathna, PhD, assistant professor of radiology at Johns Hopkins. “We developed a device to break this time barrier.”

In addition to advancing neuroimaging research, the investigators have also demonstrated a promising application involving artificial intelligence. By combining the first-ever 24-hour brain imaging dataset with video recordings of the lab animals’ behavior, the team successfully trained an AI framework to predict whether an animal was minimally mobile, moderately active, or running based solely on neuronal activity measurements made with the device. The researchers believe this approach could help scientists better understand the neurological effects of conditions such as stroke or Parkinson’s disease and potentially reveal new insights into the relationship between brain activity and behavior. Additionally, researchers say the device enables time-shared imaging from anywhere in the world, and it creates a pathway to reduce animal use while enabling neuroscientific and neuropathological insights. Lastly, CloudScope’s architecture enables “time-shared” imaging, which potentially reduces animal use.

To explore the effect of disease on different brain regions, the team plans to continue expanding the platform’s capabilities, such as imaging larger regions of the animals’ brains and leveraging AI to accelerate brain imaging and cancer cell tracking.

The post CloudScope Enables Continuous Remote Monitoring of Brain Activity in Freely Moving Mice appeared first on GEN - Genetic Engineering and Biotechnology News.

Every year, MIT Technology Review puts together a list of some of the brightest and best young minds working across science and technology. Our 35 Innovators Under 35 are the ones to watch—people whose research and technical work stands to shape the future of their fields.

This year, the list includes nine people who are transforming biotech. And this week, I’m going to give you a taste of some of the very cool stuff five of them are working on, which includes lifesaving innovations and groundbreaking “age reversal” tech.  

1. Preventing maternal deaths

Let’s start with Paschal Kija, a 28-year-old who has developed a device to treat postpartum hemorrhage—a dangerous birth complication that contributes to around 29% of maternal deaths in his home country, Tanzania. The Mkanda Salama (“Safe Wrap” in Swahili) is easy to use and costs just $70. A study found that it stopped postpartum bleeding in 73% of women within 20 minutes.

2. Making brain electrodes inspired by Japanese art

For decades, scientists have been developing, testing, and implanting brain electrodes. These devices are literally inserted into people’s brains, so while they can help us understand brain activity and treat various neurological disorders, it’s not totally surprising that they can also cause a bit of damage. Xiao Yang, 34, is working on ultra-small electrodes, which she hopes will have less of an impact on surrounding brain tissue. Her electrodes are flexible, too—in fact, they look a lot like actual neurons.

Yang is also creating sheets of electrodes to study brain cells in the lab. Inspired by kirigami—the traditional Japanese art of cutting paper to form three-dimensional shapes—she’s created a sheet of electrodes with a honeycombed structure shaped like a spiral basket. And she’s already using it to study brain cells.

3. Developing an all-new treatment for baby KJ

In 2024, Kyle “KJ” Muldoon Jr. was born with a rare and potentially fatal genetic disorder. Sarah Grandinette was a member of a team that developed an entirely new, personalized treatment for him—a gene-editing therapy essentially designed to correct a genetic misspelling.

Grandinette, who is now 26, created cells with KJ’s genetic variant and used them to screen gene-editing approaches; then she tested potential medicines in mice and monkeys. KJ ultimately got his first dose of the resulting treatment when he was about seven months old. He responded well and was eventually discharged from hospital. He’s “doing pretty great,” she says.

4. Reversing the aging process to treat eye disease

The buzziest tech in longevity right now centers on reprogramming—attempts to rewind the age of cells by resetting them to a more embryonic-like state. In a study published in 2020, Yuancheng (Ryan) Lu (now 34) and his colleagues showed that a reprogramming therapy reversed vision loss in aged, blind mice. Now an almost identical version of that therapy is being tested in people with eye disease. Life Biosciences, the company developing the drug, dosed its first volunteer in June.

5. Using AI to design new viruses

Last year, Samuel King used a generative AI model to come up with new genetic blueprints for bacteriophages—teeny viruses that can infect bacteria. Once he had those blueprints, he printed them out as strands of DNA. In experiments, he found that those AI-designed viruses could create new copies of themselves, burst out of bacterial cells, and infect other nearby bacteria. Viruses aren’t alive, but King, 27, hopes that AI-designed life forms might one day be used to make drugs or soak up pollution.

You can read more about these innovators, and the others on the biotech list, here.

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

The results showed that different cancer treatments changed the landscape of mutations in normal tissue. In particular, combined treatment using chemotherapy and radiotherapy led to significantly more normal cells with cancer-related mutations in these patients. The team suggests that sequencing normal tissue from cancer patients receiving treatment could show how our genes regulate our tissue’s response to drugs, including side effects.

Research co-lead Phil Jones, FRS, a professor of cancer development at the University of Cambridge and a senior group leader at the Wellcome Sanger Institute, said: “Our bodies are a Darwinian battleground, where cells are constantly evolving, expanding and fighting for space in our normal tissues. If you change the rules of this competition by introducing a drug, different genetic mutations are going to enable cells to win or lose. We were surprised to find that only a few weeks of cancer treatment can drastically change decades of evolution in our cells. By looking at normal tissues, we can begin to uncover how drugs work in the body, in order to make more effective treatments with fewer side effects in the future.”

Jones is co-senior and co-corresponding author of the researchers’ published paper in Nature Genetics, titled “Cancer treatment alters mutant selection in normal esophagus,” in which they stated, “Sequencing normal epithelia reveals treatment-specific selection of mutations and may identify genes implicated in cellular responses to therapy.”

Over time, all cells in the body acquire genetic changes, known as somatic mutations. While the majority of these do not affect how the cell functions, some make cells fitter, so they outcompete their neighbors. Sometimes, combinations of these mutations cause uncontrollable growth leading to cancer and the formation of tumors.

By middle age, the human esophagus has evolved into a patchwork of mutated cells. “Aging epithelial tissues, including the esophagus, are colonized by somatic mutant clones under strong competitive selection,” the authors wrote. “Mutant clones with increased fitness expand, collide and compete for space in the tissue, with only the fittest mutations surviving.” However, as the authors also pointed out, “The effect of cancer treatment on mutant selection in normal epithelium is unknown.”

By age 60 to 70 years almost all of the cells in the esophagus will be mutated. While the majority of these mutations do not lead to cancer, if tumors do form they can be hard to treat, as often symptoms appear when the cancer has started to spread.

Around 9,500 people are diagnosed with esophageal cancer in the U.K. each year, with almost half of new cases in people aged 75 and over. It is treated with surgery, chemotherapy, radiotherapy, a combination of the two—chemoradiotherapy—and immunotherapy. “We hypothesized that anticancer treatment may alter the selection of mutant clones in the already densely mutated normal esophagus,” the team commented.

For their newly reported study the Sanger Institute researchers and their collaborators set out to understand the effects of cancer treatments on normal cells, and whether chemotherapy and radiotherapy treatments give some mutant cells an advantage. The team used DNA sequencing to analyze normal cells from the esophageal lining—esophageal epithelium—that had been removed from 70 patients after treatment for esophageal cancer. The patients had either received combination chemotherapy, chemoradiotherapy, or no treatment before surgery. “The presence of normal esophagus within the surgically excised tissue gave us the opportunity to test if the mutational landscape of the normal esophageal epithelia was altered by cancer treatment using duplex, whole-genome (WGS) and targeted DNA sequencing,” they further explained.

The investigators found significant differences in genetic mutations in the cells from the patients, depending on the treatment they had received. In patients who received chemoradiotherapy, there were significantly more clones, with mutations in TP53—a vital tumor suppressor gene known as the “guardian of the genome”—and in PPM1D, a gene that makes an enzyme that manages cell stress and TP53 function.

Among patients who had received combination chemotherapy there was an increase in normal cells carrying mutations associated with resistance to the chemotherapy drug 5-fluorouracil (5-FU). The increased resilience to 5-FU in a patient’s healthy cells during cancer treatment leads to protection from life-threatening toxicities.

“These findings demonstrate that the mutational landscape of a normal epithelium that has evolved over decades may be altered dramatically in just a few weeks under the selective pressure of anticancer treatment,” they noted. “This leads to the selective expansion of preexisting mutant clones in certain treatment groups.”

Chemotherapy drugs usually leave tell-tale patterns of mutations, known as mutational signatures, in the genomes of normal tissues. Despite seeing changes in mutant cell fitness following treatments, the team found no mutational signatures associated with the chemotherapies. “The absence of a chemotherapy mutational signature in both NanoSeq and whole-genome samples of normal epithelium is notable,” they stated.

Cancer treatments can cause severe side effects in normal tissues, which may result in reducing treatment dose. The researchers suggest that their findings begin to uncover the genes and protein domains that make normal cells sensitive or resistant to treatment. The results could help shape cancer treatment in the future to help reduce damage to normal tissues. The study findings might also help inform the development of targeted treatments that destroy cancer cells while leaving normal tissue unharmed.

By identifying the mutant cells in normal tissue that are selected for by cancer treatment, the study may also provide a catalogue of potential genetic targets that modify how our cells respond to treatment, and lead to further research into how tumors become drug resistant. “… mutants in normal tissues provide in vivo evidence of actionable targets for mitigating normal tissue toxicity and may inform strategies for overcoming drug resistance in tumors,” the scientists stated.

For the next steps, the team is conducting a pilot study to investigate these effects in other tissues, taking cheek swabs, blood and urine samples from patients before and after having treatment for skin, head and neck cancers. The researchers are investigating on a larger scale, whether there is further evidence of genetic mutations in normal cells that are being selected for by cancer treatment.

Commenting on the study Hayley Brown, research information manager at Cancer Research UK, said, “People with esophageal cancer often need intensive treatment, but we still have much to learn about how these therapies affect the rest of the body. Cancer treatments can be incredibly effective, but they can also affect healthy tissues. This study gives us an unusual opportunity to see how healthy cells change during treatment, helping us understand what happens elsewhere in the body, not just in the tumor. The more we learn about these changes, the better chance researchers have of finding ways to reduce the impact of treatment on patients without making it less effective against cancer.”

The post Cancer Treatment Genetic Effects in Healthy Cells May Reveal Clues to Side Effects and Resistance appeared first on GEN - Genetic Engineering and Biotechnology News.

A Samsung Biologics’ spokesperson stated that the company’s cumulative contract value surpasses $21.9 billion following the latest agreement.

The company currently operates 845 kL of manufacturing capacity across Korea and the U.S., including 785 kL in Songdo and 60 kL at its Rockville, MD site. Acquired in March 2026, the Rockville facility established Samsung Biologics’ first manufacturing presence in the U.S., expanding the company’s global production network. Officials at Samsung Biologics say the company is also strengthening its regional presence through offices in NJ, Boston, Tokyo, and Amsterdam.

Samsung has secured land for Bio Campus III, establishing the foundation for its next phase of long-term capacity and capability expansion. The planned campus is expected to support dedicated R&D and manufacturing programs for next-generation therapeutics while the company continues to evaluate additional capacity investments in line with long-term market demand and client requirements.

Alongside capacity expansion, Samsung Biologics announced that it is pursuing opportunities to broaden its portfolio and address an increasingly diverse range of therapeutic modalities. The company has announced an all-cash offer to acquire PolyPeptide Group, which is expected to expand Samsung Biologics’ capabilities into peptide-based therapeutics and further diversify its global manufacturing network, subject to the completion of the proposed transaction.

The post Samsung Biologics Signs $262 Million Manufacturing Agreement with European Pharma Firm appeared first on GEN - Genetic Engineering and Biotechnology News.

The study is titled “Blocking PD-L2 prevents senescent cell accumulation and age-related dysfunction.” The findings, published in Cell Metabolism, point to programmed cell death ligand 2, or PD-L2, as a possible target for therapies designed to help clear senescent cells, as well as a potential blood marker for tracking their presence. Senescent cells are damaged cells that stop dividing but do not die. Instead, they can persist in tissues, where they release inflammatory factors and disrupt the function of nearby cells. Their buildup has been linked to metabolic dysfunction, impaired physical fitness, and other health problems associated with aging.

“Our findings suggest that PD-L2 may help aging cells stay in the body when they would normally be removed by the immune system,” said Selim Chaib, PhD, research assistant professor of medicine at Cedars-Sinai and first and co-corresponding author of the study.

Immune checkpoint proteins have been studied extensively in cancer, where they can help tumor cells escape immune attack. In the new study, the researchers examined whether a similar process might allow senescent cells to evade immune clearance during aging. They found that PD-L2 was increased in isolated senescent human cells and rose with age in some human tissues. Circulating soluble PD-L2 also increased with aging and declined after senolytic treatment in humans, according to the study’s highlights.

The team then tested the effects of removing or blocking PD-L2 in mice. Older mice lacking PD-L2 accumulated fewer senescent cells than older wild-type mice. They also showed greater insulin sensitivity and grip strength, two measures tied to metabolic function and physical fitness. In aged wild-type mice, anti-PD-L2 therapy restored insulin sensitivity and increased physical strength.

Together, the results suggest that PD-L2 may act as an immune checkpoint on senescent cells, helping them avoid removal and promoting their persistence during aging. The work also adds to the growing interest in senescence-targeted approaches, including senolytics, that aim to reduce the burden of dysfunctional cells rather than treating one age-related disease pathway at a time.

“If we can find a way to block this protein, we may be able to help the immune system get rid of these cells and potentially improve health problems linked with aging,” said James Kirkland, MD, PhD, director of the Center for Advanced Gerotherapeutics and senior author of the study.

The authors cautioned that more research is needed to determine whether blocking PD-L2 can safely produce health benefits in people.

The post PD-L2 Blockade May Reduce Harmful Aging Cell Buildup appeared first on GEN - Genetic Engineering and Biotechnology News.

Artificial intelligence is advancing quickly into laboratory operations, which is why thinking about the quality and integrity of the supporting data early on is important. In regulated environments, that means understanding where the data came from, how it changes, and how AI-generated insights or recommendations can be traced, reviewed, trusted, and ultimately defended.

In this GEN podcast, LabVantage’s Gary Stimson digs into what it takes to build a data foundation for trustworthy AI. The discussion covers concepts like data lineage, traceability, explainability and governance, and the importance of audit-ready laboratory operations. It also looks at the role of intended use, ongoing monitoring, and human review in deploying AI responsibly.

Podcast Guest:

Gary Stimson
Principal Architect, Head of AI Technologies
LabVantage Solutions

Produced with support from:

The post Data Integrity as the Foundation for AI appeared first on GEN - Genetic Engineering and Biotechnology News.

The project, carried out with Hal Alper, PhD, and the Alper Lab in UT Austin’s McKetta department of chemical engineering, engineered yeast to disrupt their own cell walls at the end of fermentation. This programmed lysis approach simplifies downstream processing by reducing reliance on energy-intensive mechanical disruption and removes the need for hazardous solvent-based extraction, according to the researchers.

The result, they add, is lower production costs and improved sustainability across a broad range of bioalternative products that accumulate inside cells, including lipids, proteins, vitamins, pigments, biosurfactants, and polysaccharides.

Reduced mechanical separation energy requirements

The team said they demonstrated the technology up to pilot scale (300 liters) for two industrially relevant yeasts. In Yarrowia lipolytica, engineered strains enabled a reduction in mechanical separation energy requirements by more than 50 percent. In Saccharomyces cerevisiae, the team achieved autolysis in a relevant production strain. They pointed out that the work advanced the technology from laboratory demonstration to integrated pilot operation.

“Downstream processing is one of the largest hidden costs in biomanufacturing, and it heavily influences whether a bioalternative can compete on price. By engineering yeast to disrupt their own cell walls, we reduce cost, energy, and complexity, which widens the range of products that can be made economically and sustainably at scale,” says Christine Santos, PhD, chief technology officer, Manus. By cutting processing intensity and improving recovery, these advances strengthen the case for domestic biomanufacturing.

“This work uniquely combined academic and industrial settings to take bench-scale discoveries and more rapidly translate them to higher technology readiness,” adds Alper. “This technology finally helps to address the challenge of producing cheaper intracellular products that traditionally require high-cost separations and more laborious process steps.”

The scientists note that the technology has broad application across many products that are made and accumulate inside microbial cells. By cutting processing intensity and improving recovery, these advances strengthen the case for domestic biomanufacturing built on abundant, low-cost American feedstocks.

The post Manus and UT Austin Advance Biomanufacturing Product Recovery Through BioMADE Program appeared first on GEN - Genetic Engineering and Biotechnology News.

The perspective paper, titled “Twenty-Five Years After 9/11—Lessons From the World Trade Center Health Program,” is authored by scientists and clinicians affiliated with the World Trade Center Health Program (WTC Health Program), National Institute for Occupational Safety and Health, which is part of the U.S. Centers for Disease Control and Prevention. 

It begins by highlighting some of the health effects experienced by the cohort including the fact that “many affected individuals have experienced multimorbidity” and developed multiple conditions such as “cancer, respiratory disease, gastroesophageal reflux disease, and mental disorders.” Some of these conditions developed years post-exposure “underscoring the importance of sustained clinical monitoring and research.”

Other findings from their analysis indicate that people in the cohort have a higher prevalence of both chronic conditions and poorer health-related quality of life compared to the general population. They noted that this “multimorbidity contributes to increased disability, more complex clinical management, and higher health care utilization and cost.” However, “access to no-cost care for covered conditions may improve survival, illustrating the interplay between exposure-related risk and access to care.” Elsewhere in the paper, multimorbidity is also listed as a “defining feature of care” as this population ages, although to be clear, not all their conditions are related to 9/11 exposures. The data also suggests that “integrated systems combining surveillance, clinical care, exposure assessment, and research may improve their chronic disease management.” 

Insights from the program have also shaped the patient health management strategies adopted by the program over time and expanded the list of covered conditions. As part of the study, the scientists assessed the effectiveness of the WTC Health Program in helping patients manage their conditions and improve their health outcomes. According to numbers reported in the paper, as of June 2026, more than 154,000 responders and survivors have enrolled in the program. Eligibility is based on documented occupational or environmental 9/11 exposure, and clinical coverage is limited to specific conditions described on the program’s website. 

Their analysis of program data indicates that its efforts have been largely effective. Specifically, the scientists reported  “strong performance in preventative care and chronic disease management” with screening rates for some cancers “exceeding national benchmarks.” They also found that “responders with cancer who participate in the WTC Health Program experienced 26% to 64% lower mortality rates compared with the New York State general population across multiple cancer types.” They further observed a lower smoking prevalence, about four percent, in the cohort compared to the U.S. adult prevalence of 9.1%, which “may reflect the availability and uptake of smoking cessation and related WTC Health Program services.”

The data for chronic disease management efforts was similarly positive. For people with chronic respiratory disease, “program data indicate high levels of guideline-concordant asthma management, with most members achieving an appropriate balance between controller and rescue medications,” the scientists wrote. 

Overall, there are lessons from the program that could inform future disaster response initiatives and improve public health preparedness programs among other benefits. “First, the health effects of large-scale environmental and occupational exposures may unfold over decades, requiring sustained investment in monitoring and care,” the scientists wrote. The evidence also shows that “integrated systems that link surveillance, research, and clinical care are essential for identifying and responding to emerging health risks” and “access to care at no out-of-pocket cost can help mitigate the long-term health effects of large-scale environmental exposure and support overall member well-being,” they said. 

The post What 25 Years of Research Have Revealed About 9/11’s Long-Term Health Effects appeared first on GEN - Genetic Engineering and Biotechnology News.

A Salk Institute team has now discovered a novel pathway that links chronic interferon II (IFN-II) exposure to mitochondrial dysfunction that ultimately causes immunosuppression. By explaining how interferon II turns from “good” to “bad,” the foundational insights provide a path to future therapies that combat immunotherapy resistance.

“Why interferons, which are initially anti-cancer, can become pro-cancer has been a big question in the field,” says senior author Gerald Shadel, PhD, professor and holder of the Audrey Geisel Chair in Biomedical Science at Salk. “Our study reveals a major reason for why interferons transition from ‘good’ to ‘bad,’ as well as how we can prevent this switch for therapeutic advantage moving forward.”

Shadel is senior and corresponding author of the researchers’ published paper in Science, titled “Chronic type II interferon promotes tumor growth through mitochondrial RNA–induced type I interferon and prostaglandin synthesis.”

Cancer biology and, in turn, cancer treatment have come a long way in the last few decades. Most people recognize this progress in breakthroughs like immunotherapy—a treatment strategy first deployed in 2011 that leverages the body’s own immune cells to fight cancer and revolutionized the treatment landscape. However, progress doesn’t mean all the questions have been answered.

One of those questions is why interferons that recruit the immune system to attack cancer cells can, when they linger too long, start helping the tumor grow rather than shrink. “Interferons (IFNs) are proinflammatory cytokines that promote immune cell engagement to eliminate malignant cells,” the authors wrote. “Paradoxically, chronic interferon signaling can also activate anti-inflammatory mechanisms that allow cancer cells to evade the immune system.”

Shadel’s lab has been studying interferons for a while, and for his team, the context is always mitochondria. The Shadel lab first discovered that mitochondria invoke interferon responses through the release of mitochondrial genetic material (mtDNA) into the rest of the cell. The lab’s research seeks to uncover the ways mitochondrial dysfunction can lead to inflammation, aging, and pathology.

“For this study, we turned our focus around,” Shadel explained. “Instead of asking how mitochondria affect interferons, we asked how interferons affect mitochondria. And cancer is a powerful system to ask this question in, since interferons are so essential to the body’s cancer response.”

To determine how interferons affect mitochondria the team first exposed melanoma cells to interferon I or interferon II for either acute or chronic periods. Little happened to the mitochondria on acute exposure, but chronic exposure led to measurable changes in their energetic function. The researchers then transferred these melanoma cells to a mouse model, finding that chronic interferon II exposure unexpectedly enhanced tumor growth.

The team next worked to decipher the cellular mechanisms behind the enhanced tumor growth. They found interferon II causes mitochondrial genetic material (mtRNA) to leave the mitochondria, where the rest of the cell perceives it as an invader and produces interferon I to respond. “We show that chronic type II interferon (IFN-II) exposure distinctively induced tumor growth by activating a type I interferon (IFN-I) response mediated by release of double-stranded mitochondrial RNA (ds-mtRNA) into the cytoplasm,” they noted.

Interferons I and II then work together to boost levels of the enzyme cyclooxygenase 2, which increases the synthesis of the bioactive lipid prostaglandin E2 (PGE₂). “These IFN-II and IFN-I signals then synergize to up-regulate COX2-dependent PGE2 synthesis, an immunosuppressive pathway implicated in cancer progression and chemo-, immuno-, and targeted therapy resistance,” the team continued.

If prostaglandin E₂ is causing immunosuppression, the team asked, what then happens if the melanoma cells are incapable of synthesizing PGE₂?

Anti-PD1 immunotherapies are among the most widely used immunotherapies. They work by blocking a signal that cancer cells use to keep immune cells from attacking the tumor. But tumors can also suppress the immune system through other pathways, allowing them to continue growing despite anti-PD1 treatment.

“Chronic interferon exposure is a major factor in immunotherapy resistance,” says first author Melissa Johnson, a graduate student researcher in Shadel’s lab. “We wondered whether cancer cells that have become resistant to anti-PD1 therapy were upregulating the immunosuppressive mitochondria-centered pathway we identified, and whether that pathway is a viable target for combating immunotherapy resistance.”

The researchers blocked the synthesis of prostaglandin E₂ in mouse melanoma cells. They found that eliminating this signal restored the immune system’s ability to see and fight the cancer cells. Blocking prostaglandin E₂ also reversed resistance to anti-PD1 immunotherapies. In nine of 10 mice evaluated the tumors completely regressed and didn’t return, even though they were previously resistant to immunotherapy.” Elimination of PGE₂ synthesis in immunotherapy-resistant melanoma cells restored their responsiveness to anti-PD1 treatment, indicating that this covert mtRNA-IFN-prostaglandin pathway could be a therapeutic target to combat immunotherapy resistance,” the team concluded.

The findings demonstrate potential for clinical translation in the future, offering a potential way to sustain the immune system’s attack on cancer and hope in cases of immunotherapy resistance. “Our study enriches our understanding of how the immune system attacks cancer cells but can also be stymied by other factors in the tumor environment,” said Shadel, “and also conveys the importance of integrating mitochondrial signaling functions into cancer studies.”

The post Chronic Interferon Exposure Linked to Immunosuppression in Cancer appeared first on GEN - Genetic Engineering and Biotechnology News.

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Surbhi Jain, PhD, MBBS

Staff Scientist
Bio-Rad Laboratories

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Surbhi Jain, PhD, MBBS

Surbhi Jain, PhD, MBBS, is a staff scientist at Bio-Rad Laboratories and the R&D lead for the ddPLEX EGFR/KRAS/BRAF multiplexed droplet digital PCR panel. She is focused on developing ddPCR assay solutions for precision oncology and has more than 16 years of experience in diagnostic assay development, with expertise spanning liquid biopsy biomarkers and high-throughput molecular workflows. Before joining Bio-Rad, Surbhi developed reagents for CRISPR-enabled massively parallel genome editing and served as principal investigator on SBIR programs developing cell-free DNA technologies for cancer detection and monitoring. She earned her PhD in microbiology and immunology from Temple University in Philadelphia and her medical degree (MBBS) from B.Y.L. Nair Hospital in Mumbai.

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Prithwish Pal, PhD

Director, Global Product Marketing – Oncology
Director, Global Product Marketing – Oncology

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Prithwish Pal, PhD

Prithwish Pal, PhD, is director of global product marketing for oncology at Bio-Rad Laboratories, leading the company’s ddPCR oncology portfolio for liquid biopsy, MRD, and treatment monitoring applications. With over 15 years of experience in precision oncology, he has held leadership roles in product management, market development, and medical affairs at Illumina and other diagnostics companies. He holds a PhD in biophysics from the University of Rochester and an MBA from the University of California, San Diego.

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National and international guidelines recommend biomarker testing for oncogenic driver mutations in metastatic non-small cell lung cancer (NSCLC). Emerging technologies such as Droplet Digital PCR (ddPCR) enable sensitive detection and quantification of nucleic acid targets and have been widely used in scientific research involving solid and hematologic cancer samples. Such technologies support oncology research applications, including biomarker characterization and molecular profiling studies.

In this GEN webinar, two experts will discuss the growing role of ddPCR in clinical research and translational oncology. In the first session, Prithwish Pal, PhD, will explore the use of ddPCR in liquid biopsies that require highly sensitive variant detection and precise quantification in research settings. In the second session, Surbhi Jain, PhD, will present analytical data for ddPLEX EGFR/KRAS/BRAF Mutation Detection Assay Kit*, a research-use-only kit developed for the QX600 Droplet Digital PCR System. She will share results from an external analytical validation study of the assay against alternative reference methods that showed 100% concordance in archived plasma cell-free DNA and 96.5% in FFPE specimens.

Key takeaways from the webinar include:

• Workflow and precision of ddPCR systems ideal for cancer research, including biomarker discovery, development of biomarker driven therapy, and monitoring applications in research settings
• How multiplexing extracts maximum information from limited testing research material with greater sensitivity and precision than qPCR and with less time and cost than next-generation sequencing
• A streamlined RUO ddPCR assay for metastatic NSCLC research that quantifies 37 EGFR, KRAS, and BRAF variants in a single well, paired with a mutation-agnostic total quantification well for variant allele frequency calculations.

A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelists.

*For Research Use Only. Not for use in diagnostic procedures.

Produced with support from:

The post Highly Multiplexed Droplet Digital PCR for Ultra-Sensitive NSCLC Biomarker Detection in Research Workflows appeared first on GEN - Genetic Engineering and Biotechnology News.

Among last year’s Up & Comers that are not listed this year is Charles River Laboratories. In May, Charles River completed the divestitures of its CDMO and Cell Solutions businesses to GI Partners, a private equity, real estate and data infrastructure investment firm, primarily for undisclosed contingent performance-based payments—part of a series of moves intended “to refine and further strengthen its portfolio.”

The CDMO business provided services related to the production of advanced therapies for gene-modified cell therapies, as well as gene therapies including viral vectors and plasmid DNA, while Cell Solutions provided human-derived cellular materials used for developing and producing cell therapies.

The CDMO and cell solutions businesses generated combined annual revenue of $143 million in 2025, including $117 million in the Manufacturing Solutions segment and $26 million in the Research Models and Services (RMS) segment. CRL also sold specified European assets within its Discovery Services business to IQVIA Holdings for approximately $145 million.

1. Artis BioSolutions

• Rebranded in July by combining Landmark Bio, a Watertown, MA-based development and GMP manufacturing operation, and Syngoi, a Bilbao, Spain-based enzymatic synthetic DNA business. The change unites Artis’ U.S. and European capabilities, completing a transatlantic platform linking proprietary synthetic DNA production directly to advanced therapy development and clinical-grade manufacturing.
• Emerged from stealth in April, when it disclosed its acquisition of Landmark Bio. Earlier this year, Artis acquired Syngoi, then used Syngoi’s enzymatic platform to establish new synthetic DNA manufacturing capabilities in Boston. The price of both acquisitions was undisclosed.

2. AsymBio

• Secured RMB 1.2397 billion (approximately $184 million) from Asymchem Group, Hillhouse Qirui, and other investors. The cash infusion will raise Asymchem Group’s stake in AsymBio to 83.4965%. Asymchem Group will invest RMB 1.05 billion (approximately $156 million), and Hillhouse Qirui will invest RMB 177 million (approximately $26 million).
• Generated more than RMB 140 million (approximately $21 million) in first-quarter revenue, and RMB 470 million (approximately $70 million) in revenue in 2025.

3. Bora Group

• Completed its up-to-$127.5 million acquisition of the GMP manufacturing operations, including the CDMO business, of MacroGenics—a $122.5 million deal price plus up to $5 million based on future customer orders. The transaction includes a biologics drug substance manufacturing facility located in Rockville, MD, and an associated warehousing center in Frederick, MD.
• Signed a $250 million five-year contract with GlaxoSmithKline (GSK) to renew a manufacturing partnership stretching back to when Bora purchased GSK’s Mississauga, ON, Canada, facility in 2020. The renewal will expand the companies’ partnership by allowing GSK to access multiple sites within Bora’s network, including its newest oral solid dose site in Maple Grove, MN. GSK is the largest pharmaceutical partner operating at Bora’s Mississauga facility, where Bora provides end-to-end manufacturing services for 20+ commercial product lines and 335+ individual products.

4. Curia Global

• Reached agreement on key terms of a recapitalization transaction that is expected to reinforce the company’s financial foundation and position it for long-term success. The transaction is led by funds managed by affiliates of Apollo and has the support of all of Curia’s key financial stakeholders. The deal is expected to close later this year.
• Completed a $4 million upgrade to its two aseptic suites in Valladolid, Spain. The central feature of the upgrade was the transition to a fully closed system, designed to strengthen process and product integrity while minimizing microbiological risk across all stages of production. Enhancements also focused on modernizing core equipment and systems, including installing advanced isolators, as well as upgrades to HVAC, pharmaceutical utilities, automation and sterilization-in-place processes.

5. Gland Pharma

• Executed an agreement with “one of the leading global pharmaceutical companies” for the technology transfer, manufacturing, and supply of a portfolio of sterile injectable products for global markets. The portfolio consists of oncology and non-oncology products in vials, lyophilized products, ampoules, and pre-filled syringes. The agreement covers 55 stock-keeping units (SKUs) to be manufactured across three sites, with anticipation of adding more products. Once all products are commercialized, the annualized revenue potential is expected to be approximately $90 million–$100 million.
• Launched a long-term strategic partnership with Neuland Laboratories for the manufacture of complex sterile active pharmaceutical ingredients (APIs). Gland plans to establish a dedicated sterile API manufacturing suite at its JNPC facility in Visakhapatnam, India, to support Neuland’s sterile API requirements for global drugmakers. The suite is expected to add roughly 1,400 kg (3,086 pounds) of annual production capacity and provide the flexibility to manufacture multiple sterile products.

6. Neuland Laboratories

• Completing a $20 million dedicated process development laboratory and integrated kilo lab at its Genome Valley campus in Hyderabad, India. The 135,000-square-foot facility will be made operational in phases, with full completion expected by October.
• Finished the fiscal year ending March 31 with record full-year revenues exceeding ₹2,000 crore (approximately $215 million), and EBITDA of ₹603.4 crore (about $63.4 million), up 448.6% from FY 2025. Growth was driven by commercial-stage new chemical entity (NCE) programs, particularly from North American customers, reflecting what the company said was increasing demand for reliable development and manufacturing partners for complex molecules.

7. ProBio

• Successfully delivered adeno-associated virus (AAV) scale-up materials to enable in vivo IND-enabling studies as a strategic partner to the University of California (UC) Irvine School of Medicine and GlyTR Therapeutics, developers of a next-generation AAV-mediated chimeric antigen receptor (CAR) T-cell platform, GlyTR, engineered to target tumor associated carbohydrate antigens that are highly expressed across a broad range of cancers.
• Partnered with Curocell to achieve a key CAR T milestone with Biologics License Application (BLA) approval and commercial readiness for anbalcabtagene autoleucel (anbal-cel, also known as CRC01), a next-generation CD19-targeted CAR T-cell therapy developed for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
• Expanded viral vector development capabilities at its Hopewell, NJ, site with its Viral Vector Packaging Test, a new early-stage development platform designed to accelerate decision making and derisk progression from discovery to chemistry, manufacturing, and controls (CMC) in cell and gene therapy programs. The test is designed to provide feasibility level data to support vector design, manufacturability, and scalability decisions at a critical inflection point in development.

8. Quotient Sciences

• Successful initiated a Phase I clinical study evaluating a novel drug product developed using artificial intelligence (AI). The study will assess the safety and pharmacokinetics of an undisclosed oral solid dose formulation in healthy volunteers, leveraging Intrepid Labs’ ANDROMEDA advanced machine learning algorithm to support formulation design and optimization. Quotient said the landmark achievement highlights the growing potential of AI to guide formulation design and accelerate drug development.
• Extended a commercial supply partnership with Ipsen to manufacture Sohonos® (palovarotene), a retinoid indicated for fibrodysplasia ossificans progressiva (FOP), an ultra-rare disease affecting <1,000 people worldwide. Quotient said the collaboration reinforced its commitment as a contract research, development and manufacturing organization (CRDMO) to supporting the manufacture of niche and smaller volume commercial products often overlooked by larger CDMOs.

9. Resilience

• Expanded a three-year-old strategic partnership with Eli Lilly by partnering on a $750 million expansion of its manufacturing operations in the Cincinnati region by adding to its production of Lilly’s KwikPen®device for injecting diabetes and obesity treatments. The addition will create at least 400 new jobs, bringing Resilience’s Ohio workforce to more than 1,400. Full operations are expected to start in early 2027.
• Announced plans to relocate its corporate headquarters from San Diego to Blue Ash, OH. Resilience anticipates adding approximately 200 new jobs in Blue Ash, where it also envisions basing a drug product packaging and supply operation spanning more than 450,000square feet. The move will expand an Ohio presence that includes a drug product manufacturing facility in nearby West Chester, OH.

10. uBriGene

• Launched its uVivo Lentiviral Vector (LVV) Platform, a targeted in vivo CAR T platform designed to enable precise delivery of CAR payloads to T cells, allowing rapid generation of CAR T cells in vivo. uBriGene says the platform can produce thousands of doses from a single 10 L batch.
• Initiated a strategic partnership with Cellinfinity BIO, a biotechnology company developing in vivo CAR T therapies targeting hematologic and solid tumors. The partnership is designed to accelerate the clinical advancement of Cellinfinity BIO’s therapeutic programs: CIB-301 for solid tumors and CIB-350 for hematologic malignancies and autoimmune diseases.

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While batch processing prices have risen since the pandemic and further increases are expected over the rest of this decade, the biopharma leaders concluded that their demand for outsourced services will continue to expand, especially services that increasingly depend on speed, flexibility, and specialized capabilities. Survey respondents expect the share of 2,000 liters (L) single-use bioreactor work carried out by CDMOs for both clinical and commercial supply to soon exceed 50%.

Growing customer dependence on CDMOs is reflected in a statistic published in June by Global Market Insights: The global CDMO market is projected to expand by 6.4% this year, from $173.7 billion in 2025 to $184.9 billion this year. By 2035, the market is expected to reach $342 billion, for a compound annual growth rate of 7.1%.

While access to readily available and regulatory-compliant capacity traditionally drove CDMO growth, McKinsey observed, biopharma customers are increasingly emphasizing reliability, execution, and cost competitiveness, as quality is now viewed as more of a baseline requirement than a differentiator. Quality problems can account for 15–20% of cost of goods sold, while the FDA has stepped up Form 483 violation reports by 33% last year vs. pre-COVID-19 levels. And remediation plans to address violations can cost anywhere from $10 million to $50 million.

McKinsey cited three other factors as driving CDMO decisions among customers: Growing pressure to improve operational performance and productivity, rising cost sensitivity among customers, and what McKinsey termed “surprisingly thin” loyalty to CDMOs.

“Failing to bridge the gap”

“This suggests that many CDMOs are failing to bridge the gap from physical capacity and baseline execution to the productivity needed for competitive pricing,” according to McKinsey.

Other CDMO market watchers such as Imen Jelassi, PharmD, founder and CEO of life sciences business development consultancy Corstrate, cite the ongoing reshoring of manufacturing operations by Western biopharmas wrought by the BIOSECURE Act as presenting a potential opportunity for U.S. and European CDMOs.

Below is GEN’s updated A-List of Top 10 CDMOs. The companies are ranked by 2025 revenues, as disclosed by the companies in regulatory filings or in responses to GEN’s queries. Several of the CDMOs have also furnished quarterly or half-year revenues for 2026. For the first time, GEN offers a year-over-year revenue comparison that offers another interesting insight: Eight of this year’s top 10 CDMOs recorded year-over-year revenue increases, with combined revenue of the top 10 growing to $35.116 billion in 2025, up six percent from $33.127 billion in 2024.

As with last year’s A-List, GEN also spotlights 10 “Up & Coming” CDMOs that are not yet large enough to rank within the top 10, based on recent news announcements ranging from facility openings to significant contracts (online only).

Unlike the 2025 CDMOs A-List, this year’s rankings no longer include Catalent because it no longer publicly reports its revenues—a result of the Bridgewater, NJ-based CDMO having been acquired for $16.5 billion by Novo Holdings, the asset manager of the foundation that controls Novo Nordisk, in a deal completed on December 18, 2024.

Just missing the top 10, at No. 11, is Merck KGaA, Darmstadt, Germany, whose Life Sciences business in the U.S. and Canada goes by the name MilliporeSigma. Merck KGaA/MilliporeSigma saw its CDMO revenue fall 8.7% year-over-year, to €659 million ($761 million) last year from €722 million ($834 million) in 2024. The company hopes to reverse that decline through activity in new facilities such as its €300 million ($345 million) Bioprocessing Production Center in Daejeon, South Korea, that is set to open by year’s end, and its new €25 million ($29 million) 2,000-square-meter (21,528-square-foot) BioReliance^® testing facility in Darmstadt, Germany, which opened in July.

All dollar figures for 2024 revenues differ from the figures reported by GEN in last year’s A-List of Top 10 CDMOs due to currency fluctuations.

#1. Lonza Group

Basel, Switzerland

2025 Revenue: CHF 6.531 billion ($8.053 billion) ¹

2024 Revenue: CHF 6.574 billion ($8.106 billion) ²

% Change: — 0.7%

Finished H1 2026 with EBITDA of CHF 1.175 billion ($1.449 billion), up 27 from CHF 922 million ($1.137 billion) in H1 2025, on revenue that grew 16% year-over-year to CHF 3.374 billion ($4.160 billion) from CHF 3.034 billion ($3.741 billion).¹

Considering construction of a $1 billion plant on two parcels totaling 161 acres on land owned by Clermont County, OH, in Williamsburg Township, some 25 miles east of downtown Cincinnati. On June 29, the Ohio Tax Credit Authority approved a 1.860%, 20-year Job Creation Tax Credit for the project, which would create 650 full-time-equivalent positions. Ohio is competing for the project against Texas, North Carolina, and Virginia.

Announced an expanded strategic collaboration with an undisclosed “leading U.S.-based biopharmaceutical company.” The expansion adds two biologics programs to be produced commercially, with the option for two more, and further strengthens an established multi-year relationship, including long-term commitments across a broad portfolio of multiple biologics programs.

Disclosed plans to enhance its drug-linker center of excellence and expand payload-linker manufacturing capacity at its site in Visp, Switzerland. The expansion will establish new commercial-scale capabilities for the manufacture of highly complex and highly potent active pharmaceutical ingredients (HPAPI) and ADC payload-linkers.

#2. Thermo Fisher Scientific

Waltham, MA

2025 Revenue: $7.142 billion ³

2024 Revenue: $7 billion ⁴

% Change: +0.2%

Opened a new bioanalytical and biomarker laboratory in Gothenburg, Sweden, located within GoCo Health Innovation City. The new facility expands the company’s global bioanalytical and biomarker service capabilities to support pharmaceutical and biotechnology customers across all phases of drug development.

Introduced the Gibco CTS DynaXS Single Use Bioreactor, a purpose-built expansion platform designed to help cell therapy developers scale manufacturing with precise control, flexibility, and regulatory readiness. The bioreactor is designed to support flexible, cGMP-ready cell expansion from process development to clinical production to support the development of cell therapies.

Opened its flagship U.S. Bioprocess Design Center (BDC) at the company’s Plainville, MA, site, expanding the facility to support customers in developing and scaling biologics. The new center brings together advanced bioproduction capabilities and hands-on collaboration, with the aim of helping customers accelerate process development and bring therapies to patients faster.

#3. WuXi AppTec

Shanghai, China

2025 Revenue: RMB 45.45 billion ($6.737 billion)

2024 Revenue: RMB 39.241 billion ($5.816 billion)

% Change: +15.8%

Finished H1 2026 with adjusted non-IFRS net profit of RMB 11.57 billion ($1.715 billion), up 83.2% year-over-year, on revenue that climbed 38.9% from H1 2025, to RMB 28.90 billion ($4.284 billion). For the first time, WuXi AppTec revenue surpassed that of Lonza Group.

Obtained a preliminary injunction from U.S. District Chief Judge James Boasberg, appointed to the federal district bench in 2011 by President Barack Obama, temporarily blocking the U.S. Department of Defense from designating WuXi AppTec as a “Chinese military company.” Washington has alleged the company is indirectly owned by China’s State-owned Assets Supervision and Administration Commission and indirectly affiliated with China’s State Administration of Science, Technology and Industry for National Defense (SASTIND) and People’s Liberation Army.

Raised full-year 2026 revenue guidance to RMB 58.5 billion to RMB 60.5 billion ($8.672 billion to $8.968 billion), up 10.4% to 14% from previous guidance of RMB 51.3 billion to RMB 53.0 billion ($7.604 billion to $7.855 billion), with continuing operations revenue raised to 35% to 39% year-over-year, up from 18% to 22%.

Raised 2026 capital expenditure or “capex” guidance range to RMB 7.5 billion to RMB 8.5 billion ($1.112 billion to $1.260 billion), up 13.3% to 15.4% from RMB 6.5 billion to RMB 7.5 billion ($963.5 million to $1.112 billion) to support accelerated global capacity expansion, including initiation of a new Changzhou, China, site ahead of schedule.

#4. WuXi Biologics

Wuxi, China

2025 Revenue: RMB 21.790 billion ($3.230 billion)

2024 Revenue: RMB 18.675 billion ($2.768 billion)

% Change: +16.7%

Agreed to acquire CDMO assets in Hangzhou, China, from Transcenta Holding for RMB 190 million (approximately $28.2 million), reflecting the buyer’s pivot from physical manufacturing to developing its core biomanufacturing platforms and technologies: “The Company does not consider the provision of CDMO services a core part of its principal business,” Transcenta stated in a Hong Kong Exchange regulatory filing.

Marked the development of its 1,000^th molecule on its integrated contract research, development, and marketing organization (CRDMO) platform, a trispecific antibody for ophthalmic diseases that is being developed under a partnership with Earendil Labs.

Secured FDA Pre-License Inspection (PLI) approval for its MFG8 drug substance manufacturing facility in Hebei, China, which is equipped with twelve 4,000 L single-use bioreactors and offers flexible commercial manufacturing at scales ranging from 4,000 L to 20,000 L. The facility supports commercial manufacturing for an undisclosed “potential blockbuster” autoimmune therapy.

#5. Samsung Biologics

Incheon, South Korea

2025 Revenue: KRW 4.557 trillion ($3.222 billion)

2024 Revenue: KRW 4.547 trillion ($3.215 billion)

% Change: +0.2%

Finished Q2 with consolidated operating profit of KRW 586.4 billion ($414.6 million), up 23% year-over-year, on KRW 1.321 trillion ($933.9 million) in revenue, up 30% from Q2 2025.

Launched an all-cash public tender offer to acquire PolyPeptide Group, a Baar, Switzerland-based CDMO specializing in peptide-based active pharmaceutical ingredients (APIs), for approximately CHF 1.46 billion ($1.803 billion). The transaction is expected to be completed toward the end of 2026.

Completed the $353 million acquisition of its first manufacturing site in the U.S., a Rockville, MD, facility, from GlaxoSmithKline (GSK). The Rockville site consists of two cGMP manufacturing plants with a combined 60,000-liter drug substance capacity, supporting both clinical and commercial biologics production across multiple manufacturing scales.

Secured land for BioCampus III, laying the groundwork for future capacity expansion to support next-generation therapies and emerging modalities.

#6. Boehringer Ingelheim

Ingelheim, Germany

2025 Revenue: €1.470 billion ($1.697 billion) ⁵

2024 Revenue: €1.235 billion ($1.426 billion)

% Change: +19.0%

Selected the osapiens HUB for Maintenance as the frontline mobile platform for its maintenance teams to plan, execute, and document production-critical maintenance work across its regulated manufacturing operations, using a single solution to plan, coordinate, execute, and close out work.

Cut €900 million ($1.039 billion) in planned domestic spending and investments in Germany for 2027–2030, blaming German government plans to cut healthcare spending and require drug developers to grant higher discounts on treatments to insurers. “We have to keep pace with developments in the USA and Asia,” Médard Schoenmaeckers, head of BI’s German division, told German business news outlet Handelsblatt.

Launched a new center for artificial intelligence (AI) and machine learning in King’s Cross, London, U.K., part of the company’s goal of advancing AI for pharmaceutical research and development. The U.K. site adds to BI’s Computational Innovation footprint, which includes locations in Austria, Germany, and the U.S. specializing in AI, machine learning, human genetics, and computational biology.

#7. Siegfried

Zofingen, Switzerland

2025 Revenue: CHF 1.328 billion ($1.640 billion)

2024 Revenue: CHF 1.295 billion ($1.599 billion)

% Change: +2.5%

Appointed Eduardo Montanha as COO and member of the Executive Committee, effective September 1. Montanha was previously executive vice president, head of global technical operations and quality at Fresenius Kabi.

Named Frédéric Kahn as head of global business development and sales, drug products. Kahn joins Siegfried from Piramal Pharma Solutions, where he was vice president of business development for Europe and the rest of the world.

Inaugurated a new large-scale production facility for API manufacturing in Minden, Germany. The facility adds 100 cubic meters (3,531 cubic feet) of reactor capacity and is designed to strengthen Siegfried’s position as a leading global CDMO for small molecule drug substances.

Completed acquisition of three Noramco Group companies from SK Capital Partners for “below 10 times Enterprise Value / EBITDA.” The deal involves three small-molecule drug substance sites with about 400 employees: Noramco, a commercial-scale manufacturing site in Wilmington, DE; Purisys, a clinical API development and manufacturing facility in Athens, GA; and Extractas Bioscience, a manufacturer of purified products in Westbury, Tasmania, Australia.

#8. Fujifilm Biotechnologies / Fujifilm Corp.

College Station, TX / Tokyo, Japan

2025 Revenue: ¥257.2 billion ($1.616 billion) ⁶

2024 Revenue: ¥219.5 billion ($1.379 billion)

% Change: +17.2%

Appointed Maja Pedersen as president, in addition to her role as COO, as part of a planned leadership succession with Lars Petersen transitioning from his role as president and CEO, effective immediately, to strategic advisor through September 30.

Celebrated the selection of its commercial-scale cell culture manufacturing facility in Holly Springs, NC, among seven facilities chosen by the FDA for its PreCheck Pilot Program, designed to strengthen the nation’s pharmaceutical manufacturing capabilities.

Opened a new, 2,000‑square‑meter (21,528-square-foot) quality control (QC) laboratory at its Hillerød, Denmark, commercial‑scale manufacturing site. The expanded QC footprint is designed to enable bioassay and virology operations to meet current and future customer demand and support the site’s planned expansion.

Opened its expanded site in Teesside, U.K., funded through a total investment of approximately £400 million ($540 million) from parent Fujifilm Corp. The expanded site includes the opening of the largest single-use biopharmaceutical CDMO facility in the U.K., a 110,000 square-foot manufacturing facility that introduces 2,000 L and 5,000 L single-use bioreactors with a total capacity up to 19,000 L to provide small- and mid-scale antibody manufacturing.

#9. Recipharm

Stockholm, Sweden

2025 Revenue: €837 million ($966 million) ⁷

2024 Revenue: €827 million ($955 million)

% Change: +1.2%

Announced a multi-million-dollar investment in its U.S. operations, designed to strengthen its ability to support pharmaceutical and biotechnology companies with advanced sterile fill and finish services for biologics and advanced therapies.

Launched a strategic collaboration with Fusix Biotech to support the development and GMP manufacturing of next-generation oncolytic virus-based cancer immunotherapies, starting with Fusix’s lead candidate FUSE102, a chimeric oncolytic virus encoding a high-affinity soluble PD-1 intended to enable immune checkpoint inhibition and strengthen anti-tumor activity.

Disclosed a multi-million investment in a new Blow-Fill-Seal (BFS) manufacturing line, expanding capacity to support customer programs from development through commercial supply. The expanded capacity will support a broad range of ophthalmic product programs.

#10. AGC Biologics / AGC Group

Seattle, WA / Tokyo, Japan

2025 Revenue: Y129.420 billion ($813.253 million) ⁸

2024 Revenue: ¥137.326 billion ($862.958 million)

% Change: -5.8%

Secured half the mammalian manufacturing capacity of its new Yokohama, Japan, facility through a multi-year contract with a “large pharmaceutical company” that is expected to reach hundreds of millions of dollars in value. AGC Biologics agreed to manufacture a minimum of 35 batches per year of five biopharmaceutical products for the undisclosed customer.

Entered a strategic partnership with Pyramid Pharma Services that combines its sterile fill-finish capabilities with AGC’s drug substance development and manufacturing expertise. The integrated offering also includes device assembly, labeling, and secondary packaging services for clinical programs.

Selected by Japan-based transdermal drug delivery technology developer Teikoku Seiyaku to provide microbial contract development and manufacturing services for KTP-001, a recombinant human matrix metalloproteinase-7 (rhMMP-7), to treat lumbar disc herniation.

References

1. Financial information presented for Lonza reflects its continuing CDMO business without the Capsules & Health Ingredients (CHI) business, which Lonza has agreed to divest by selling it to Lone Star Funds for CHF 2.3 billion ($2.836 billion), in a deal set to close by year’s end.
2. 2024 results consist of sales from all operations, since CDMO business results had not been separated in Lonza’s financial results until 2025. CDMO operations excluded Capsules & Health Ingredients segment, which is not figured into CDMO results.
3. This Thermo Fisher figure, confirmed by a spokesperson, is based on “Pharma Services” activity accounting for ~29% of the $23.984 billion in revenue generated in 2025 by the company’s Laboratory Products and Biopharma Services segment. The “29%” percentage was disclosed by Thermo Fisher during its most recent Investor Day, held May 20, in a presentation that stated that the segment generated $24.4 billion in revenue for the 12 months ending March 31.
4. This Thermo Fisher figure was disclosed during the company’s Investor Day held September 19, 2024, in a presentation that stated “$7B Revenue” as being generated by the Pharma Services business of Thermo Fisher’s Laboratory Products and Biopharma Services segment. Through a spokesperson, Thermo Fisher last year confirmed that figure as its most accurate value of 2024 CDMO activity.
5. This Boehringer Ingelheim figure reflects revenue for the company’s BioXcellence division (biopharmaceutical contract production), furnished by the company within its annual reports.
6. This Fujifilm Biotechnologies figure is the sum of Q1–Q4 fiscal year 2025 quarterly revenue figures for the “Bio CDMO” business within the Healthcare segment of Fujifilm Holdings, whose subsidiaries include CDMO Fujifilm Biotechnologies—rebranded in 2025 from Fujifilm Diosynth Biotechnologies. Fujifilm operates on a fiscal year that runs from April 1 of the named FY to March 31. FY 2025 covers the 12 months starting April 1, 2025, and ending March 31, 2026.
7. Does not include £299 million ($403 million) in revenue reported by S&P Global to have been generated in 2025 by the former inhaled and nasal drug-device business, which was spun out of Recipharm into Bespak through a process completed in April 2024.
8. Figure consists of Life Science Operations segment revenue for calendar year as published by AGC Group, which rebranded itself from Asahi Glass Company Ltd. in 2018.

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“HCD brings differentiated human cell models that complement Revvity’s broad portfolio of technologies supporting drug discovery and development,” said Prahlad Singh, president and CEO of Revvity. “As researchers continue to seek more human-relevant approaches to understanding biology, combining high-quality cell models with our capabilities in screening, detection, automation and analysis creates an opportunity to provide customers with more integrated solutions.”

HCD’s flagship EndoC-βH5 human pancreatic beta cell model is designed to provide researchers with a human-relevant model for studying beta cell physiology and function across diabetes and obesity research. HCD also offers specialized media and reagents, preclinical research, and its NatLine cell-line development platform, which was developed to support the development of functionally consistent human cell models.

“Human Cell Design was founded on the belief that better human models can help transform the way medicines are discovered and developed,” said Guillaume Costecalde, founder and president of Human Cell Design. “Joining Revvity is expected to allow us to bring our human cell models and NatLine technology to a broader global customer base while supporting the development of new physiologically relevant cell models.”

The combination aligns with Revvity’s portfolio of detection and cell analysis technologies, according to a Revvity officials, who adds that EndoC-βH5 cells are well-suited for use with Revvity’s HTRF and AlphaLISA assays for measuring key pharmacological readouts such as cAMP and insulin as well as pHSense technology for receptor internalization studies.

The combination also extends to Revvity’s ATPlite assays for cell viability and proliferation analysis. These detection and analysis capabilities are expected to extend to Revvity’s high-content screening platform and methods for interpreting complex cellular data. As wet-lab validation becomes increasingly important to support AI-enhanced science, human-relevant cell models provide an important foundation for testing and confirming AI-generated insights.

Revvity also notes that HCD’s technology also has applications beyond early-stage discovery, including research supporting regenerative medicine approaches for Type 1 diabetes and quality control activities as cell-based therapies progress toward commercialization.

The post Revvity Signs Agreement to Acquire Human Cell Design appeared first on GEN - Genetic Engineering and Biotechnology News.

Cell and gene therapies, including CAR T-cell therapies, are expected to become increasingly important treatment options for cancer and other intractable diseases. In Japan, however, expanding the availability of specialized manufacturing personnel and manufacturing facilities remain significant challenges, underscoring the need for a more robust and sustainable supply framework.

Under the joint research agreement, Shinshu University Hospital’s expertise in CAR T-cell therapy R&D and clinical application will be combined with Teijin Regenet’s manufacturing and quality-management expertise cultivated through its CDMO business for regenerative medicine products. The partners said they will work together to enhance manufacturing technologies and strengthen the manufacturing base for cell and gene therapies.

The collaboration will also utilize the Cell Processing Center (CPC) at Shinshu University Hospital to explore future manufacturing automation and efficiency improvements. In addition, the partners will work to accumulate practical knowledge related to quality testing technologies and quality-control methodologies.

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Cell culture has come a long way since then.

Today, media optimization is a sophisticated scientific discipline that influences nearly every aspect of cell culture, from academic research to commercial biomanufacturing. The composition of a culture medium affects cell growth, productivity, product quality, impurity profiles, downstream purification, and, ultimately, manufacturing economics. As biologics manufacturers pursue increasingly intensified production processes, optimizing media has become one of the industry’s most important—and most complex—challenges.

That complexity was the focus of a recent discussion with Bhanu Chandra Mulukutla, PhD, research fellow and group leader at Pfizer, and Wenge Wang, PhD, associate research fellow and group leader at Pfizer.

“The first challenge is understanding more about the cells you’re dealing with and the product you’re trying to make,” says Mulukutla. “Growth characteristics, metabolism, impurity profiles, and product requirements all influence how media should be optimized.”

Different production cell lines, such as CHO and HEK293 cells, have distinct nutritional needs and metabolic behaviors. A formulation that performs well for one therapeutic protein might be far from optimal for another. Developers must simultaneously balance multiple priorities, supporting robust cell growth while maximizing productivity, preserving product quality, minimizing impurities, and ensuring downstream purification remains efficient.

Beyond simply adding more nutrients

One of the biggest misconceptions in media development is that adding more nutrients automatically produces better results. In reality, every nutrient has an optimal operating window.

“Cells sense nutrient levels,” Mulukutla explains. “Too little is obviously bad, but too much is also bad.”

Even glucose, one of the most fundamental energy sources, becomes problematic when supplied in excess. Elevated nutrient concentrations can trigger metabolic shifts that reduce productivity, alter protein quality, and generate unwanted waste products.

The challenge becomes even greater as manufacturers intensify production processes. Higher-performing cell cultures require significantly greater nutritional support, but physical chemistry imposes practical limits. Several amino acids—including tyrosine, cysteine, leucine, isoleucine, and valine—have relatively poor solubility, making it difficult to formulate increasingly concentrated media.

Developers frequently reach a point where desired nutrient concentrations simply cannot dissolve. That limitation creates a cascade of manufacturing complications. Additional feeds become necessary. Mixing procedures become more complex. Filtration slows because of increased viscosity. Preparation times lengthen, and precipitation risks increase.

In other words, media optimization is constrained not only by biology, but also by chemistry and manufacturing practicality.

Intensification raises the stakes

These challenges become even more significant in intensified fed-batch manufacturing. Unlike conventional fed-batch processes, intensified operations drive cultures to much higher viable cell densities while sustaining elevated productivity over longer production runs.

That combination dramatically increases nutritional demand. Maintaining adequate nutrient availability without excessive feed additions becomes a delicate balancing act. Because all nutrients cannot be supplied in a single highly concentrated formulation, manufacturers often rely on multiple feeds, particularly for poorly soluble amino acids like tyrosine and cysteine. Meanwhile, branched-chain amino acids—leucine, isoleucine, and valine—present another obstacle, because cells consume them rapidly while their solubility remains relatively low. As nutrient requirements increase, formulation complexity grows accordingly.

Even when adequate nutrition is supplied, another challenge begins to emerge—waste accumulation. Unlike perfusion systems, intensified fed-batch processes continually add nutrients without removing spent media. Over 12 to 14 days, metabolic byproducts steadily accumulate. Those byproducts can inhibit cell growth, reduce productivity, and negatively influence product quality. Host-cell proteins can also reach elevated concentrations, creating additional purification challenges and potentially affecting product stability.

As the Pfizer experts note, the objective is no longer simply maximizing titer. Developers must simultaneously optimize productivity, cell health, impurity control, manufacturability, and final product quality.

Engineering better cells

Rather than focusing exclusively on media composition, Pfizer has adopted a broader systems-level strategy. After nearly a decade of studying cellular metabolism using omics technologies and systems biology, researchers have identified pathways responsible for generating problematic metabolic byproducts. That understanding has enabled entirely new engineering approaches.

One strategy involves carefully maintaining nutrient concentrations near the lower end of their healthy operating ranges. “When nutrients aren’t in excess,” Mulukutla says, “cells are smart enough to use them for their intended purpose—growth and protein production—rather than funneling them into byproduct formation.”

Another approach directly modifies cellular metabolism. Pfizer researchers have engineered cells by knocking out key enzymatic steps in pathways responsible for producing unwanted metabolic waste. For branched-chain amino acids, eliminating the first step in their breakdown pathway reduced cellular consumption by approximately 30 to 40%. Instead of converting those amino acids into waste products, engineered cells use nutrients more efficiently.

The benefits extend beyond metabolism. Reduced amino-acid demand frees valuable osmolality capacity within the media, allowing scientists to incorporate higher concentrations of other nutrients needed for intensified production.

Perhaps the most intriguing strategy addresses one of media optimization’s oldest challenges. Instead of trying to dissolve more tyrosine and cysteine into increasingly concentrated feeds, Pfizer researchers engineered cells to make them capable of intracellularly synthesizing those amino acids.

Using more soluble precursor molecules—specifically, synthesizing tyrosine from phenylalanine and cysteine from methionine—engineered cells generate their own supplies of these otherwise difficult-to-deliver nutrients. The approach reduces dependence on highly concentrated external feeds while simplifying formulation.

Combined with reduced byproduct formation and improved nutrient efficiency, these engineered cell lines support higher cell densities without proportionally increasing media complexity. Pfizer is now integrating multiple engineering strategies into unified production cell lines designed to support intensified manufacturing across its broader biologics portfolio.

AI-driven design

Media optimization is also becoming increasingly data driven. Rather than treating media development as an isolated upstream activity, the Pfizer experts envision a fully integrated development strategy that simultaneously considers cell engineering, upstream processing, and downstream purification.

Future optimization efforts will likely rely heavily on artificial intelligence and advanced computational modeling. These technologies can help researchers understand complex metabolic networks, predict nutrient requirements, optimize formulations, and identify opportunities that traditional experimentation might overlook.

The long-term goal is ambitious. Instead of requiring complex perfusion systems to achieve very high cell densities, future mammalian cell lines might eventually approach the metabolic and stoichiometric efficiency currently associated with microbial production systems, enabling higher yields in standard or intensified fed-batch conditions.

In the nearer term, alternative nutrient-delivery strategies are also showing promise. Dipeptide versions of difficult amino acids, including tyrosine-glycine, have been shown to dramatically improve solubility compared with free amino acids. Although these formulations introduce higher material costs and additional supply-chain considerations, they provide valuable flexibility while complementary cell-engineering approaches continue to mature.

Building flexible platforms

One of the most important considerations for any cell culture is ensuring the consistency of the raw materials used to make the media, according to Martin Gawlitzek, PhD, director of bioprocess development at AbbVie. Because media formulations rely on numerous ingredients sourced from different suppliers, even subtle differences—particularly in metal impurities—can influence critical quality attributes and process performance. Close collaboration with media manufacturers and rigorous testing programs are therefore essential to maintaining lot-to-lot consistency and reliable biologics production.

To address these challenges, AbbVie developed a high-performance, modular media platform that supports a wide range of manufacturing strategies, from traditional fed-batch production to intensified bioprocesses. The platform is designed to achieve high cell densities while providing the flexibility to fine-tune product quality attributes. “The same platform can be tailored for different bioprocesses and easily adjusted to modulate product quality,” Gawlitzek explains. As a result, AbbVie can leverage a common foundation across multiple programs with minimal modifications.

“Media development fundamentally involves continuous improvement,” Gawlitzek says. “Our near-term focus is to further optimize our platform to accommodate emerging therapeutic modalities, particularly complex molecules like multi-specific antibodies, which often have distinct media requirements for optimal expression and product quality.”

Industry-wide innovation

The rapid evolution of media optimization extends well beyond individual organizations. Several presentations at the 2026 18th Bioprocessing Summit in Boston reflect how broadly the field is advancing.

Novasign highlighted digital twins that combine mechanistic process models, artificial intelligence, and manufacturing data to improve media optimization, scale-up, and end-to-end process control.

Biogen presented strategies for converting conventional production platforms into intensified fed-batch processes using smart media design, N-1 perfusion, and process analytical technology, demonstrating significant improvements in manufacturing efficiency while maintaining product quality.

Meanwhile, RedShift Bio showcased analytical technologies that provide real-time, chromatography-grade titer measurements directly within upstream workflows, enabling faster feeding decisions and improved bioreactor control.

Together, innovations from AbbVie, Pfizer, and others illustrate how the future of cell culture will depend less on simply feeding cells more—and more on understanding how to help them use every nutrient more intelligently. That integrated approach, combining smarter cells with smarter media and smarter process design, could define the next generation of biomanufacturing.

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Their models are increasingly capable of processing long clinical records, interpreting complex terminology, comparing documentation against evidence and generating coherent summaries from large volumes of information. For clinicians, operators, and administrative teams who spend significant time searching through fragmented data, these advances are helping reduce cognitive burden and make high-value information easier to access.

But healthcare leaders should not confuse model capability with operational capability.

Healthcare’s administrative challenges are caused by fragmented information, fragmented workflows, and fragmented accountability, not a lack of information. The industry has spent decades investing in systems that capture activity: electronic health records, billing platforms, payer portals, scheduling systems, call center platforms, and analytics applications. Each system records something important. But few were designed to reason across the full chain of decisions that determines whether patients get timely access, clinicians have the right documentation and providers are reimbursed appropriately.

This is the problem that AI must now confront.

Revenue cycle is becoming one of healthcare AI’s proving grounds

The revenue cycle is the process healthcare providers use to get paid for care — from scheduling and registration through coding, billing, payer follow-up, and payment collection.

It is unusually suited to rigorous AI deployment because it combines high transaction volume, complex reasoning, structured and unstructured data, measurable outcomes, and significant operational variation. It also sits at the intersection of financial performance, patient access, and administrative workload.

A single claim can be influenced by patient insurance information, clinical documentation, coding rules, payer-specific policies, prior authorization requirements, medical necessity criteria, and many other data sources and operational processes. A breakdown in any one of those areas can create downstream consequences weeks or months later.

This is why generic automation has often fallen short.

Traditional robotic process automation works well when workflows are stable and rules are predictable, but healthcare administration is neither. Payer requirements change. Documentation expectations evolve. Exceptions are common and often material.

Large language models improve part of the equation, extracting meaning from narrative text, summarizing records and supporting reasoning over complex documentation. But when used alone, they inherit important limitations. They may produce plausible outputs without sufficient traceability. They may lack awareness of local workflow constraints. They may miss payer-specific history or context that determines whether an action is likely to change an outcome.

Why foundation models will become necessary but insufficient

The major AI firms are solving real technical problems for healthcare.

Better context windows make it easier to process longitudinal records. Stronger reasoning improves the interpretation of complex clinical scenarios. Better multimodal capabilities may eventually help connect text, imaging, structured data, and clinical signals in more useful ways. Safer model behavior and healthcare-specific tuning will continue to improve adoption.

These capabilities will make healthcare work faster, more consistent and easier to navigate. But they will not, on their own, solve deep-rooted administrative complexity.

Much of healthcare’s operational knowledge does not live in general medical literature, coding manuals, or public payer guidance. It lives in the accumulated experience of what actually happens after decisions are made. For example:

• Why does one appeal strategy outperform another?
• Which documentation gaps are most likely to cause reimbursement delay?
• How does a specific payer respond to a particular clinical argument?

These insights are behavioral, operational, and longitudinal. They emerge from years of transactions, outcomes, exceptions, and human judgment.

As foundation models become more capable, access to baseline healthcare knowledge will become less differentiating. Most leading systems will be able to interpret ICD-10 codes, recognize medical terminology, summarize payer policies, and reason over public clinical criteria. The durable advantage will come from how organizations combine that model intelligence with proprietary operational data, structured knowledge, workflow context, and governance.

The technical shift: From automation to orchestration

Agentic orchestration turns foundation model understanding into coordinated action — intelligence that can follow work across systems, apply the right rules, adapt when something changes, and keep learning from what happens next.

A prior authorization workflow, for example, may require retrieving clinical documentation through fast healthcare interoperability resources (FHIR) APIs, mapping patient history to payer criteria, identifying missing evidence, generating a submission packet, routing exceptions to a specialist, monitoring payer response, adjusting patient care pathways, and learning from the outcome.

This type of workflow requires coordination. It also requires guardrails: regulatory requirements, privacy standards, clinical policies, coding rules, payer criteria, and organizational risk thresholds. One promising approach is hybrid architecture that combines LLMs with structured knowledge bases, symbolic logic, reinforcement learning, and deterministic validation layers.

At Ensemble, this is the design principle behind EIQ, our revenue cycle intelligence engine. EIQ brings together operational activity, clinical documentation, payer behavior, and reimbursement outcomes into a continuously learning intelligence layer that’s integrated with the hospital’s electronic health record (EHR). It supplements the system of record with a system of intelligence, designed to connect information and surface actions most likely to improve outcomes.

EIQ uses a neuro-symbolic approach that combines LLMs and custom small language models with rules-based reasoning. That architecture is built on one of the most robust datasets in healthcare, informed by more than a decade of award-winning operational performance, transaction history, payer behavior, and operator decision-making. The language models help interpret information and generate human-readable outputs. The symbolic layer represents policies, rules, payer requirements, and workflow constraints so the system can apply guardrails, make reasoning steps more traceable and recommend actions that fit the specific operational context.

What the next decade will reward

The contribution of major AI firms to healthcare will be significant. Their models will become faster, safer, more capable, and more accessible.

But the next decade of healthcare AI will be defined by integration, not model capability alone.

The organizations that create the most value will be those that connect models to governed data, operational workflows, domain expertise, human oversight, and measurable outcomes. They will understand that healthcare intelligence cannot live in a separate interface. It has to exist inside the decisions that shape access, documentation reimbursement, and patient experience.

This content was produced by Ensemble. It was not written by MIT Technology Review’s editorial staff.

Researchers evaluated automated 600-µL RoboColumns operated on a Tecan liquid-handling platform against conventional, roughly 20-mL ÄKTA bench-scale chromatography models and manufacturing-scale operations for purification of a bispecific antibody (bsAb). The goal was to determine whether the two scale-down approaches provided equivalent process understanding or introduced scale-dependent biases.

The work covered three purification operations: lambda light-chain affinity, anion exchange, and cation exchange chromatography. The researchers first qualified both scale-down models against manufacturing data and then replicated multivariate design-of-experiments studies across the Tecan and ÄKTA systems.

The attraction of miniaturization is significant. High-throughput purification tools offer “parallelization and material savings” compared with traditional bench-scale experiments and can “enable practical end-to-end integration to automate entire experiment workflows,” Rezvani and his colleagues note.

The results strengthen the argument for extending those benefits deeper into bioprocess development. RoboColumn scale-down models showed “excellent agreement with manufacturing scale at target operating conditions” and aligned with bench-scale results from multivariate studies, according to the authors. Perhaps more important for process characterization, the practical effect of differences between the two models on the resulting control strategy was “negligible,” wrote Rezvani and his colleagues.

That does not mean that microscale chromatography behaves identically to larger systems. Smaller working volumes, offline fraction analysis, intermittent liquid delivery, and differences in flow behavior can introduce variability. In the study, step yields and product column volumes “consistently varied between” scale-down models (SDMs), the researchers point out, although product-volume offsets were highly reproducible across broad process parameter ranges. As the authors emphasize, a “well-characterized SDM does not need to produce data that is identical to manufacturing scale” to be suitable. Instead, differences need to be understood, their risks assessed, and appropriate offsets or controls incorporated into the manufacturing strategy.

There are still practical limitations. The researchers recommend maintaining product-pooling consistency, minimizing evaporation effects, and ensuring sufficient product volumes for reliable analytical testing. For processes showing unusual or highly sensitive host-cell protein washes or protein recovery, they suggest additional microscale characterization or hybrid studies combining microscale and traditional bench-scale experiments. Plus, qualification remains essential. “Comparability to manufacturing scale must be verified through proper SDM qualification and scientific rationale,” the authors caution.

Taken together, the study shifts the question from whether microscale chromatography perfectly reproduces larger columns to whether its differences can be predicted and managed. The researchers reported that RoboColumn differences were “predictable both at target conditions and across varied process parameter ranges” for three chromatography methods commonly used in antibody manufacturing. For bioprocess teams facing increasingly complex biologics and pressure to accelerate development, that finding could move microscale chromatography beyond a screening tool—and closer to a platform for generating the process understanding behind commercial manufacturing decisions.

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Making cell therapies is always complex. The sensitive raw materials must be protected, production plants need to comply with GMP regulations, and the therapies have to be prepared so they retain potency until they reach the patient.

However, for autologous, patient-specific cell therapies, the operational challenges are particularly significant, says Zhaowei Li, a researcher and PhD student at the H. Milton Stewart School of Industrial and Systems Engineering at the Georgia Institute of Technology.

“Making an autologous cell therapy is not universally more difficult than an allogeneic therapy, because allogeneic products have their own biological and manufacturing challenges. Operationally, however, autologous manufacturing is especially demanding because each patient represents an individual batch.

“Patient-specific starting material, end-to-end chain of identity, and the time-sensitive coordination of collection, manufacturing, release, and return all create substantial logistical complexity. Unlike an allogeneic product, an autologous dose generally cannot be replaced from inventory if production is delayed or fails,” he tells GEN.

Operational options

To address these challenges, autologous cell therapy developers have several potential options, according to Li and colleagues who examined the topic in a recent study published in Biotechnology and Bioengineering.

They looked at three models: centralized production in a single facility; a coordinated point-of-care (POC) network in which POCs coordinate the transfer of materials and consumables; and an independent network in which each POC operates separately.

Choosing the optimal option depends on the specifics of the project, Li says, citing a coordinated POC network by way of example.

“Under our baseline assumptions, coordinated POC manufacturing provides a strong compromise between cost and turnaround time. In a coordinated POC network, sites share real-time information on patient specimens, reagent inventory, and manufacturing capacity. A network coordinator can then redirect specimens or reagents when a local shortage or capacity constraint would otherwise delay treatment.

“In our case study, coordinated POC manufacturing remained within approximately 1.2% of the centralized system’s expected cost while reducing average turnaround time from 29.5 to 28.2 days. Independent POC manufacturing was slightly faster, at 27.5 days, but approximately 43.5% more expensive,” he says.

Li adds, “Coordinated POC may not be preferable when demand is low or geographically concentrated, centralized transportation is reliable and inexpensive, or the cost and regulatory burden of operating multiple qualified manufacturing sites outweighs the turnaround-time benefit.

“Its success also depends on reliable data sharing, cross-site quality consistency, governance, and the practical feasibility of transferring specimens or reagents between sites. Our findings should therefore be viewed as decision support under specific assumptions rather than a one-size-fits-all prescription,” he says.

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For biomanufacturers, this suggests the possibility of a practical screening strategy to identify factors that could enhance expression levels or improve specific product attributes for certain genes expressed in CHO cells. Applicability to HEK293 or PER.C6 cells has not been studied.

Pabpc is considered crucial in mRNA stability and translation, and Pabpc1, specifically, extends the half-life of target mRNAs and orchestrates mRNA stability and pre-mRNA splicing. “Up to now, no studies have investigated the impact of Pabpc1 gene overexpression on recombinant protein production in CHO cells,” note Zhangying Jia, research scientist; Zheng Zhang, PhD, head of cell line development; Jing Song, PhD, vice president of biologics technical development; and colleagues at BeOne Medicines. This research offers insights regarding Pabpc1 that may enhance CHO cell expression in a production setting.

Jia and colleagues overexpressed Pabpc1 in a variety of low-expression clones used to produce monoclonal, bispecific, and trispecific antibodies. Growth rates were essentially identical to those of cells transfected with an empty vector, which served as the control. Of the three types of antibodies produced, expression level gains were greatest among bispecific antibodies, showing a 50% productivity increase. Trispecific antibodies showed a 32% productivity increase, and mAbs showed a 30% productivity increase. Other quality attributes were virtually identical between the overexpressed and control groups.

Additionally, “We discovered that Pabpc1 overexpression can modulate cellular metabolism to some extent,” according to the team. Consequently, lactic acid and ammonia accumulation were each lower in the overexpression groups than in the control groups. “These findings suggest that Pabpc1 overexpression may have a positive effect on regulating cellular metabolism by reducing the accumulation of toxic by-products… thereby creating a more favorable environment for protein production,” the scientists posit.

The team also reports an interaction between Pabpc1 and the eukaryotic initiation factor 4E (eIF4E) that catalyzes subsequent reactions, leading to enhanced efficiency of translation initiation.

The enhanced productivity for both individual cells and overall titer that resulted from overexpressing Pabpc1 “is highly contingent upon the congruence between [a gene’s] functions and the intrinsic productivity bottlenecks of host cells,” they observed, noting that none of the other five genes that were overexpressed during this study (Slc25a32, Il19, Ptdss1, Stk3, and Mtdh) showed comparable results.

Exactly how overexpression of Pabpc1 enhances productivity of recombinant proteins in CHO cells “remains to be fully elucidated,” the scientists point out, but this strategy appears to be both novel and efficacious and offers “substantial potential for industrial application.”

The team plans to continue refining this strategy and broadening its applicability for biopharmaceutical manufacturing.

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Scientists headed by a team at the University of Texas Health Science Center at Houston have now developed monoclonal antibodies (mAbs) targeting matrix metalloproteinase-9 (MMP-9), which in a newly reported preclinical study slowed and even reversed diabetic nerve damage in mouse models of type I diabetes (T1D) and type II diabetes (T2D). The team suggests that their results bring researchers one step closer to developing a treatment for humans.

Research lead Xin (Alex) Ge, PhD, professor in the Texas Therapeutics Institute at The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases within McGovern Medical School at UTHealth Houston, is senior and co-corresponding author of the team’s published paper in Science Translational Medicine, titled “Monoclonal antibodies inhibiting MMP-9 activity alleviate peripheral neuropathy in diabetic mice.”

Up to 50% of diabetes patients will develop peripheral neuropathy, which is the most common chronic complication of diabetes, the authors wrote. “The hallmark of diabetic peripheral neuropathy (DPN) is the length-dependent damage of peripheral nerves because of impaired microvascular circulation and mitochondrial dysfunction,” they explained. In addition to pain, tingling or numbness, symptoms may include loss of balance, slow wound healing and foot ulcers. However, the team further noted, “Despite its substantial impact, there are currently no effective disease-modifying treatments available to prevent or reverse the progression of nerve damage.”

Ge stated, “There is no good drug for managing peripheral neuropathy. There are painkillers and other drugs, but they are only targeting the symptoms.” For their reported study the investigators focused on the enzyme MMP-9. This enzyme can break down other proteins found between tissues. It is responsible for excess immune response in the peripheral nervous system and disease progression that impairs wound healing. “By regulating neuroinflammation, matrix metalloproteinase-9 (MMP-9) is both sufficient and required for the pathogenesis of neuropathy, representing a promising drug target for DPN,” they commented. “However, small-molecule inhibitors that often lack target specificity.”

Ge and the team instead developed monoclonal antibodies targeting MMP-9. “Developing an antibody that selectively targets MMP-9 has been challenging because MMP-9 is closely related to other enzymes,” acknowledged first author Kibaek Lee, PhD, a postdoctoral research fellow at the Institute of Molecular Medicine. “To overcome this challenge, we combined a camelid-inspired antibody library design with a functional selection approach to identify antibodies that specifically inhibit MMP-9. These new biotechnologies separate our antibodies from others.”

In preclinical tests mice injected with the antibodies regenerated nerve fiber and showed improved wound healing in their paws. “MMP-9 mAbs also reduced epidermal nerve fiber degeneration in diabetic mice by enhancing nerve mitochondrial function and promoting skin angiogenesis,” they stated.

“ This gives us hope that we can not only relieve the symptom, but also reverse the progression of disease,” said Ge, who holds the Kay and Ben Fortson Distinguished Chair in Neurodegenerative Disease Research at McGovern Medical School.

In addition, the team showed also showed that MMP-9 expression in human dorsal root ganglia (DRG) is increased among patients with diabetes. Further human genetic analysis found that both rare and common coding variants in the MMP9 gene are associated with neuropathic pain phenotypes. “The translational relevance of this study is supported by the observation that MMP-9 expression is increased in satellite glial cells and macrophages in the DRG of patients with T2D,” they stated. “Together, these translational findings indicate that MMP-9–specific mAbs hold potential as disease-modifying therapies for peripheral neuropathy and for reducing lower extremity complications associated with diabetes.”

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Now, in a new study, gene therapy delivered intravenously extended the lifespan and reduced symptoms in a cat model of Sandhoff disease. The findings could extend the potential of gene therapy to treat Sandhoff and Tay-Sachs disease, both of which are marked by toxic accumulations of fat in nerve cells of the brain and spinal cord.

This work is published in Science Translational Medicine in the paper, “Intravenous gene therapy improves lifespan and clinical outcomes in a feline model of Sandhoff disease.”

Previous clinical trials showed that adeno-associated virus (AAV) gene therapy for Sandhoff disease could be delivered by injection into the brain or cerebrospinal fluid. More specifically, previous studies “have led to the development of an adeno-associated virus (AAV) vector–delivered gene therapy for children with GM2 gangliosidosis in both expanded access and Phase I/II clinical trials through intrathalamic and cerebrospinal fluid–based delivery.” But intravenous AAV gene therapy has not been evaluated until now.

The AAV gene therapy tested in this study expressed the two Hex enzymes that have been implicated in Sandhoff disease. (Hex consists of two subunits, α and β, encoded by the HEXA and HEXB genes, respectively.) Deficiencies in these enzymes prevent the breakdown of waste in nerve cells’ lysosomes, leading to the toxic fat buildup.

The study investigated intravenous delivery of a bicistronic AAV vector–based gene therapy that has not yet been tested in clinical trials to a feline model of Sandhoff disease, treated presymptomatically at one month of age.

In the feline Sandhoff models, intravenous delivery of the AAV gene therapy was safe and efficacious, and cats treated with a low dose lived two times longer than untreated cats; cats treated with a high dose lived three times longer. The authors write, “whereas untreated SD cats lived to 4.3±0.2 months, SD cats treated with low or high doses of the gene therapy lived to 8.3±1.2 or 12.4±2.7 months, respectively.”

The treatment also led to marked improvement in body tremors, reduced markers of central nervous system damage, and improved liver damage in the high-dose treatment group. “These data support the dose-dependent efficacy of IV-delivered gene therapy for restoration of Hex activity and preservation of clinical metrics, supporting potential for translation to patients with SD,” the authors note.

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Many patients are diagnosed at advanced stages (III/IV) when the disease has metastasized, resulting in poorer prognoses and clinical outcomes. Improving patient outcomes requires technological advancements that enable early detection when the disease is localized (stages I/II). However, effective screening options for many cancer types remain limited.

Novel approaches are urgently needed to improve availability and accessibility of diagnostic assays and, to that end, recent efforts in the field have shifted toward uncovering the biological pathways and molecular profiles underlying disease onset, progression, and metastasis.

Liquid biopsy, a minimally invasive blood-based technology that detects tumor-derived biomarkers, has the potential to detect cancer at earlier stages (I/II) and positively impact patient survival. Many liquid biopsy assays are under development or in the early stages of commercial availability, and are designed to detect mutations, methylation patterns, and/or fragmentation patterns in circulating tumor DNA (ctDNA) by next-generation sequencing (NGS)-based technologies.

However, limitations remain due to complexity and cost, and their performance for early-stage cancer detection remains largely unproven.

Powerful tools for oncology

A technology that offers the opportunity to rise above these limitations is mass spectrometry. MS-based omics approaches (the study of all biological molecules within an organism, grouped into subdisciplines such as proteomics, lipidomics, and metabolomics; the study of all proteins, lipids, and metabolites, respectively) have emerged as powerful tools for oncology, particularly for liquid biopsy-based early detection. Thanks to its high sensitivity, specificity, and accuracy over other technologies, MS allows for the identification and quantification of a wide range of molecules from small metabolites to larger proteins.

Over the past few decades, MS-based proteomics has matured into a robust, high throughput platform with ever-increasing resolution and acquisition speed, enabling the quantification of thousands of proteins and mapping of the proteome across multiple cancer types. In fact, genetic mutations common across multiple cancer types alter the proteins produced from such genes, leading to changes in cellular function that support pro-cancer cellular activities.

As a result, proteins serve as the critical link between the genotype and the phenotype of a disease. On the clinical front, MS-based proteomics is now used for other disease detection and therapeutic monitoring applications due to its multiplexing capacity and high throughput over conventional methods.²   Therefore, the stage is set for MS to deliver proteomics-based profiles for oncology-based applications as well.

Profiling the metabolome and lipidome

More recently, MS is being leveraged to profile the metabolome and lipidome, providing insight into tumor metabolism and the surrounding microenvironments. Metabolomics is widely regarded as the omics discipline that most closely reflects the snapshot of the disease phenotype, as metabolites and lipids reflect the cumulative changes occurring due to alterations in the genome, transcriptome, and proteome. Changes in these blood-based molecules, therefore, hold untapped potential for early-stage cancer diagnostics.

Of all the omics disciplines, the newest kid on the block is lipidomics, which has experienced research-based growth in the last few years thanks to major advances in MS technology and bioinformatics tools such as machine learning. Lipidomics can provide a highly detailed, personalized, and quantitative snapshot, capturing thousands of lipid species within a single liquid biopsy.

Lipids are critically linked to cancer biology, and the study of the lipidome allows for the characterization of lipid molecules and their roles in biological pathways and mechanisms tied to cancer development and metastasis.³

Through standardization and harmonization efforts,⁴ lipids have now become highly adaptable to clinical diagnostics.⁵ Whether individually or when combined with proteins and metabolites, lipidomics offers the potential for a powerful new tool in clinicians’ toolbox for early cancer detection: by characterizing the lipidome alongside the proteome and metabolome of patients with cancer, we can start to untangle the mechanisms that drive cancer biology.

From there, novel candidate biomarkers can be identified and ultimately translated into clinically actionable diagnostic endpoints.

At AOA Dx, Abigail McElhinny, PhD, is CSO, and Rachel Culp-Hill, PhD, serves as senior product scientist. Kim Ekroos, PhD, is founder and CEO at Lipidomics Consulting.

References

1. Global cancer burden growing, amidst mounting need for services.

2. Birhanu, A. G. Mass spectrometry-based proteomics as an emerging tool in clinical laboratories. Clin. Proteomics 20, 32 (2023).

3. Hou, M. et al. The strategic role of lipidomics in biomarker identification and diagnosis of gynecological diseases. Front. Endocrinol. 16, 1546512 (2025).

4. McDonald, J. G. et al. Introducing the Lipidomics Minimal Reporting Checklist. Nat. Metab. 4, 1086–1088 (2022).

5. Ekroos, K. et al. Lipid-based biomarkers for CVD, COPD, and aging – A translational perspective. Prog. Lipid Res. 78, 101030 (2020).

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Del-desiran failed the Phase III HARBOR trial (NCT06411288) by missing the study’s primary endpoint of statistically significant improvement vs. placebo in video Hand Opening Time (vHOT) through week 54. vHOT is a frequently used measure of hand myotonia, according to a 2024 study, and involves clinical experts reviewing videos to measure the time from hand grip to opening.

However, Novartis added that it saw evidence of clinical activity in exploratory analyses and secondary endpoints—which included hand grip strength and quantitative Muscle Testing composite score, both measured by dynamometer; MD1 activity and participation scale; and 10-Meter Walk/Run Test. Safety findings from HARBOR were generally consistent with previously reported data, according to Novartis.

Novartis did not disclose details of its data but said it is evaluating the full dataset from the HARBOR trial and will engage with authorities to determine the most appropriate development path for del-desiran.

“Developing therapies for a complex disease like DM1 remains challenging, and setbacks are part of scientific progress,” Shreeram Aradhye, president, development and chief medical officer, Novartis, said in a statement. “As we continue to evaluate the full HARBOR dataset, we remain committed to identifying the most appropriate development path for the del-desiran program and advancing innovative approaches for people living with DM1 and other serious neuromuscular diseases.”

Third clinical setback in a week

Del-desiran’s failure marked Novartis’ third clinical setback in a week. On Friday after the closing bell, the company and partner Ionis Pharmaceuticals acknowledged that their co-developed pelacarsen failed the Phase III Lp(a)HORIZON trial (NCT04023552) by missing its primary endpoint of reducing the risk, compared with placebo, of cardiovascular events—a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization.

And on September 2, Novartis paused eight trials assessing its autoimmune and neurological disease candidate rapcabtagene autoleucel (rap-cel), after three patients treated with the personalized, CD19-directed chimeric antigen receptor T cell (CAR T) therapy died after experiencing immune effector cell-associated hemophagocytic syndrome.

Four of the trials were within Novartis’ Phase II AUTOGRAPH program, assessing rap-cel in systemic lupus erythematosus and lupus nephritis (NCT06581198), idiopathic inflammatory myopathies (NCT06665256), diffuse cutaneous systemic sclerosis (NCT06655896), and ANCA-associated vasculitis (NCT06868290). The other four were Phase I/II studies in forms of multiple sclerosis (NCT06617793 and NCT06675864), myasthenia gravis (NCT06704269), and rheumatoid arthritis and Sjögren’s disease (NCT07048197).

As a result, investors did not appear to share Novartis’ apparent optimism on del-desiran on Tuesday, instead punishing the company for its latest pipeline failure with a stock selloff that sent its shares trading on the SIX Swiss Exchange tumbling 11% from CHF 125.46 ($155.01) to CHF 111.80 ($138.13)—the pharma giant’s worst one-day decline since March 2020, early in the COVID-19 pandemic.

On the New York Stock Exchange, Novartis’ American depositary shares fared worse, dropping 14% from $159.99 to $137.72.

Del-desiran is an AOC candidate designed to target the underlying cause of DM1. The therapy consists of a muscle-targeting monoclonal antibody that binds to the transferrin receptor 1 (TfR1) and is conjugated to a small interfering RNA (siRNA) designed to induce degradation of disease-causing toxic DMPK messenger RNA (mRNA). Del-desiran has received the FDA’s Orphan Drug, Fast Track, and Breakthrough Therapy designations, as well as the European Medicines Agency’s Orphan Medicinal Product Designation.

Inherited from Avidity

Del-desiran is one of three pipeline AOCs that Novartis inherited when it acquired Avidity Biosciences for $12 billion in a deal completed February 27 and still among this year’s largest biotech acquisition transactions. In addition to del-desiran, Novartis acquired delpacibart zotadirsen (del-zota), an Exon 44-targeting AOC designed to treat Duchenne muscular dystrophy (DMD) and delpacibart braxlosiran (del-brax), an AOC intended to treat facioscapulohumeral muscular dystrophy (FSHD) by targeting DUX4.

Del-zota is under evaluation in the Phase II EXPLORE44OLE (NCT06244082) trial following completion in November 2024 of the Phase I/II EXPLORE44 (NCT05670730) study. Del-brax is being assessed in the Phase III FORTITUDE-3 trial (NCT07038200). In June, Novartis trumpeted positive data from the FORTITUDE Phase I/II trial (NCT05747924) of del-brax, saying the study’s biomarker cohort met its primary and key secondary endpoints, with reductions in KHDC1L (cDUX) and creatine kinase biomarker levels indicating both strong target engagement and reduction in muscle damage in patients with FSHD.

In acquiring Avidity, Novartis sought to justify the deal by noting that Avidity’s AOCs held potential to develop into therapies with sizeable annual sales. On the day it announced the deal, Novartis raised its expected 2024-2029 sales compound annual growth rate (CAGR) from +5% to +6%,“representing a significant opportunity to deliver substantial shareholder returns over time,” the company stated in its press release, and said the deal would bolster its mid-single-digit long-term growth.

Speaking with CNBC in July, Novartis CEO Vas Narasimhan projected peak year sales of “$5 billion-plus,” while analyst forecasts for del-brax hovered in the $2 billion range, though projections for del-zota called for peak sales ranging between $315 million and $450 million.

Avidity had aligned with the FDA on a path toward accelerated approval for del-zota, while del-desiran and del-brax were on track to be the first globally approved drugs for their respective conditions.

“Avidity’s pioneering AOC platform for RNA therapeutics ​and its late-stage assets bolster our commitment to delivering innovative, targeted, and potentially first-in-class medicines to treat devastating, progressive neuromuscular diseases,” Narasimhan said in a statement at the time.

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In a paper titled “HRAS promotes mutant NRAS–driven transformation with codon and allele specificity,” Hyun Lee, a PhD candidate at the Uniformed Services University of the Health Sciences, and colleagues investigated how different NRAS mutations shape cancer signaling and treatment sensitivity. The study examined how mutant NRAS works with nonmutant, or wild-type, RAS proteins to sustain oncogenic signaling.

To isolate these interactions, the researchers used mouse cells lacking all RAS proteins and studied the effects of expressing mutant NRAS with or without reintroduced wild-type RAS family members. This system allowed the team to test whether mutant NRAS could drive transformation on its own or whether it required help from other RAS proteins. “Global dependency mapping in human cancer cells revealed functional partitioning, wherein mutant NRAS promoted MAPK signaling and wild-type HRAS promoted PI3K-AKT survival signaling,” they added.

The results showed that mutant NRAS proteins do not all behave the same way. NRAS mutations at glycine residues—G12X and G13X—retained some GDP-GTP cycling and showed modest autonomous transforming potential. By contrast, Q61X mutations, which lock NRAS in an active GTP-bound state, were more dependent on wild-type RAS for receptor tyrosine kinase–stimulated signaling and oncogenesis. Among the wild-type RAS proteins, HRAS emerged as a particularly important partner: reintroducing wild-type HRAS was sufficient to restore signaling and transformation in RASless cells expressing mutant NRAS.

The study also suggested that mutant NRAS and wild-type HRAS divide the labor of oncogenic signaling. Mutant NRAS primarily promoted MAPK signaling, while wild-type HRAS supported PI3K-AKT survival signaling. That functional split created therapeutic vulnerabilities, but the most effective drug combinations varied by NRAS mutation. Pan-RAS(ON) and HRAS inhibition showed synergy across the NRAS mutants tested, with Q61X mutants particularly sensitive to the combination. For G12X and G13X mutants, however, adding inhibitors of proximal RAS regulators such as SOS1 or SHP2 was needed to more fully suppress proliferation.

Together, the findings argue against a one-size-fits-all approach to NRAS-mutant cancers and support mutation-guided combination strategies that account for both the mutant allele and its wild-type RAS partners. As the authors wrote, “These findings define the signaling partnership between mutant NRAS and wild-type HRAS as a targetable vulnerability and provide a biochemical blueprint for dual RAS inhibition in NRAS-mutated malignancies.”

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The development and use of biologic-based immunotherapies is one of the fastest-growing areas in the biopharmaceutical sector. These immunotherapies use different mechanisms of action (MoA) and formats, including chimeric antigen receptor (CAR) T cells, monoclonal antibodies (mAbs), and antibody drug conjugates (ADCs).

A crucial step during immunotherapy development is verifying MoA through delivery of the cytotoxic payloads to the targeted cells in a heterogeneous environment. The streamlined Promega HiBiT Target Cell Killing (TCK) platform is a bioluminescent cell-based system that measures cytotoxicity with specificity, simplicity, and sensitivity during therapeutic development. The mix-and-match platform supports broad immunotherapy modality assessment for four killing mechanisms—CAR-T cell-mediated killing, antibody-dependent cellular cytotoxicity (ADCC), T cell-dependent cellular cytotoxicity (TDCC), and antibody-dependent cellular phagocytosis (ADCP).

Off-the-shelf, thaw-and-use HiBiT target cells express an intracellular HiBiT peptide that remains stable in media for >3 days with minimal leakage and is released only upon cell death. Released HiBiT binds cell-impermeable LgBiT to form functional NanoBiT luciferase, generating a bright, quantitative signal. The luminescent signal is proportional to target cell death alone, with no contribution from effector cells, making the platform ideal for co-culture experiments.

The HiBiT TCK platform leverages gain, not loss, of signal detection. This approach avoids the kinetic complications of loss-of-signal assays, where prolonged luminescence decay can obscure cell death timing and complicate endpoint selection. The simplified no wash, load, or staining workflow produces robust signal-to-noise with as few as 2,000 cells in 96-well formats or 500 cells in 384-well formats.

Thaw-and-use target cells

A growing library of off-the-shelf assay components includes thaw-and-use, functionally tested cell lines that address blood cancer targets, including B cell lymphoma and leukemia, myeloid leukemia, and multiple myeloma (Raji, Ramos, H929), as well as solid tumor targets for ovarian carcinoma (OVCAR3), breast adenocarcinoma, and lung carcinoma (SKOV3, SK-BR-3). HiBiT-containing target cell lines can also be custom tailored using ViaScript^® transfection.

For cell lines not in the standard panel, the ViaScript (HiBiT) TCK Bioassay enables rapid screening of target cells using transient HiBiT expression. ViaScript is a novel mRNA transfection reagent that enables rapid and titratable transient expression of HiBiT mRNA in a wide range of adherent or suspension target cell types for early high-throughput screening and clone selection. The transfected cell lines can be screened simultaneously and used in a HiBiT TCK Bioassay and paired with qualified primary effector cells and a biologic to measure ADCC, ADCP, TDCC or CAR-T cell killing. Once optimal TCK lines are identified with the ViaScript (HiBiT) TCK Bioassay, Promega’s Tailored R&D Solutions (TRS) offers custom clonal line development.

Off-the-shelf primary effector cells

Promega’s primary effector cells provide a consistent and robust method for target cell killing. The primary effector cells are MoA-qualified to measure the potency and stability of antibodies and other biologics that specifically bind and activate their respective effector cells. Stocked as thaw-and-use products, primary effector cells are functionally tested with the HiBiT Target Cell Killing Bioassays. PBMCs are ADCC-qualified, CD8+ T cells are TDCC-qualified, and macrophages are ADCP-qualified to assess Fc effector-driven activity. Effector cells are available in two product formats: as standalone vials or in bioassay kits.

The homogeneous, sensitive HiBiT TCK platform and bioassay provides a robust assay window for four immunotherapy killing mechanisms. The versatile mix-and-match platform supports experiments with different combinations of effector and target cells. The resulting luminescent signal is specific to target cell killing, making the bioassay well-suited for mixed co-culture experiments during development efforts. The HiBiT TCK platform supports ADCC with PBMC effectors, TDCC with CD8+ T cells, ADCP with macrophages, and CAR-T killing assays across a 4–72-hour time course.

Explore More promega.com/products/reporter-bioassays/target-cell-killing-bioassays.

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Surprises that delay manufacturing programs tend to arrive late in the day. A comparability package will not close if reactor scale-up, site transfer, or cell-line improvement produces a new analytical signal that cannot be reconciled with the material dosed in the clinic. Each of those changes was deliberate, yet the divergence it produced was not. What looks like an analytical problem can reflect an underlying product or process change.

A council of separate assays

The quality of a biologic is conventionally assessed not by one instrument but by a council of specialists, each fluent in one dialect. Charge variants speak through imaged capillary isoelectric focusing, size variants through size-exclusion chromatography, glycans through released-glycan mapping, and identity and modifications through peptide mapping.

Each specialist instrument is an expert, and each offers a partial answer. Across the years from candidate to commercial supply, that council is reconvened as methods, instruments, and qualified reference standards change. What survives is not a story but a stack of testimonies; the seams between them are where late surprises are born.

One framework, one language

The multi-attribute method (MAM) offers a more coherent approach: a peptide-mapping LC-HRMS (liquid chromatography-high resolution mass spectrometry) workflow that can identify and monitor multiple product quality attributes, including selected critical quality attributes, and resolve modifications to specific sites. In a single analysis, MAM can monitor deamidation, oxidation, site-specific glycoforms, sequence variants, and other product-related features, potentially streamlining quality control across the product lifecycle.

MAM is built in two movements: a broad characterization phase that identifies measurable attributes and assembles a product-specific peptide library anchored by accurate mass and retention time; and a monitoring phase that tracks the relative abundance of selected attributes, batch after batch.

Catching what no one thought to ask

MAM’s distinctive capability is new peak detection, a threshold-based comparison that aligns mass, retention time, and intensity features against a product-specific reference and flags new or significantly changed peaks for review. A conventional release assay reports within its intended analytical dimension. New peak detection asks a broader question: has an unexpected peptide-level feature changed?

Detecting that signal while the process is still being developed, rather than after it is locked, can be valuable because the attribute that ultimately matters may not be the one predicted.

When the process changes

Consider a typical crisis: a perfusion process replaces fed-batch, a step is redesigned, and a campaign moves to a second manufacturing site. Regulators require evidence that relevant quality attributes remain highly similar and that observed differences do not adversely affect safety or efficacy. Assembled from scattered legacy assays, that evidence can require substantial time to build and still show its seams.

When the same peptide mapping-based framework has traveled with the molecule from its earliest characterization, comparability can become less of an emergency and more a continuation of an established data stream. The peptide-level reference and historical attribute data already exist. That continuity can strengthen the broader comparability package.

What MAM does not solve

MAM is not a universal solution. By separating the molecule into peptides, MAM does not directly assess aggregation, particles, higher-order structure, biological activity, or modification combinations on the same intact molecule. It also depends on robust data analysis. MAM has been implemented for release in specific applications, and USP <1060> now provides a practical framework, while broader implementation continues to evolve. MAM works best as a backbone for directed attribute monitoring, supported by orthogonal methods.

Analytical continuity by design

At Catalent’s Kansas City analytical center of excellence, MAM and high-resolution mass spectrometry are applied as independent analytical services, supporting programs wherever the molecule is manufactured. Against a decade of process change, the aim is not more testimony, but a single coherent account, and fewer places for the story to break.

Comparability is easier to defend when it never had to be reconstructed.

Learn more about Catalent Biologics Analytical Services.

www.Catalent.com

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RNAV8, a biofirm applying AI-driven design and laboratory validation to engineer more predictable mRNA medicines, will be part of a team led by the Rouskin Lab at Harvard Medical School with the Weissman Lab at MIT/the Whitehead Institute. The award, a one-year ARPA-H pilot of up to $4.4 million, will fund a program to turn RNA’s natural folding behavior into a precise, drug-tunable control layer for a new generation of RNA medicines. PROPEL is led by ARPA-H program manager Shannon Greene, PhD.

“The promise of mRNA has always been that it’s programmable, but in practice the relationship between a RNA’s sequence and chemistry and what it actually does has been hard to predict,” said Devan Shah, founder and CEO of RNAV8 Bio. “Our work with the Rouskin and Weissman labs is aimed squarely at that gap: learning the rules that connect sequence to function, and building them into logic-gated constructs that express where and when they should.

“Just as important, every element we discover stays answerable in the format a medicine actually ships in. We’re proud to help carry this science from a regulatory element toward a real therapeutic.”

Within PROPEL, RNAV8 Bio focuses on the therapeutic format itself. It screens protein output from pools of transfected mRNA, engineers UTRs in the delivery format, and validates results at the cargo level, for example driving cell-type-selective expression of therapeutic payloads such as gene-editing enzymes or CAR constructs.

PROPEL pursues a different kind of control

Most medicines act wherever their chemistry carries them, and most genetic therapies work by permanently changing DNA. PROPEL pursues a different kind of control. An RNA molecule’s untranslated regions (UTRs) fold into structures, and those structures set how much protein the message produces. When a small molecule binds one of those folds, the structure rearranges and the output changes, turning a dose into a dial on protein expression, without altering the genome. Bacteria use this logic openly, in elements called riboswitches; in human cells it remains largely uncharted.

“For decades we’ve read RNA sequence as a set of instructions for making a protein. What we can now read, at the scale of thousands of sequences at once, is how that sequence folds, and how a small molecule can change the fold and, with it, the output,” said Silvi Rouskin, PhD, assistant professor of microbiology, Harvard Medical School. “Human cells almost certainly already use this kind of structural control; we’ve simply never had the tools to find it systematically. PROPEL is our attempt to map it and put it to work.”

Engineering installs regulatory elements into therapeutic mRNA so that a single construct is selective by cell type through its sequence and tunable through its structure. Both rely on high-throughput mapping of how a RNA’s folds shift when a ligand binds, which flags the elements that regulate protein output before the team tests which ones a small molecule can move.

The Weissman Lab contributes massively parallel screens of human untranslated-region elements across cell types, measuring which ones set expression where.

“The untranslated regions flanking a message are among the most powerful and least exploited levers on how much protein a cell makes,” said Jonathan Weissman, PhD, professor of biology, MIT and member, Whitehead Institute. “By screening these elements across cell types, we can begin to tell which ones set expression where, turning a vague notion of ‘regulation’ into a defined, reusable parts list. That is what makes a control layer generalizable rather than a one-off trick.”

By the end of its initial phase, the collaboration aims to produce resources that do not exist today: a map of how thousands of human RNA sequences respond to small molecules, with structural models; a ranked catalogue of human UTR elements that set translation cell type by cell type; engineered UTRs that reach meaningful selectivity in a therapeutic format; and RNA sequences, natural or engineered, shown to switch structure inside human cells. Together these are meant to form a generalizable, disease-agnostic foundation for RNA medicine, according to the scientific team.

PROPEL is a program supported by ARPA-H that develops a programmable, drug-tunable control layer for RNA medicines.

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Immunotherapies have dominated cell and gene therapy for the past 5–10 years, but the field of regenerative medicine is gaining momentum. Mesenchymal stem cells (MSCs) remain central to this field, with expanding applications as direct therapies and as producers of MSC-derived extracellular vesicles (MSC-EVs). This article examines the biological and regulatory factors shaping their promise.

MSC Therapies: Promise, Frustration, and a Push Toward Biomarkers to Drive Efficacy

MSC therapies show strong biological promise, but translation remains slow because efficacy and consistency are difficult to demonstrate. A key priority is aligning therapy design with MSC biology. Autoimmune diseases, such as progressive multiple sclerosis, are strong applications because treatment options are limited and early studies suggest MSCs may help reset immunity. Experts recommend biomarker-driven trials to identify appropriate patients earlier and improve evaluation. MSCs are often misunderstood and underutilized, making biomarker-driven design and global harmonization essential for success.

MSCs are attractive because they can be used in allogeneic therapies: donor cells can be cryopreserved, thawed, and used off-the-shelf to treat larger patient populations, including autoimmune and cardiovascular indications. Developers are moving toward 3D culture systems to increase production, simplify manufacturing, and enable MSC-EV generation. However, shifting from 2D to 3D culture systems can alter confluency, marker profiles, EV productivity, and other critical quality attributes. Teams must optimize media, serum or HPL, additives, and reagents to maintain CQAs at scale.

Process changes in media, microcarriers, or feed schedules can dramatically affect MSC performance, increasing interest in AI-driven optimization of consumables and reagents. As 3D systems advance, developers still rely on serum or HPL to support cell health and consistency, while the industry increasingly demands chemically defined, serum-free systems. Better serum-free and HPL-free solutions are needed for clinical development of MSC therapies and MSC-EVs. Together, these trends show MSC therapies becoming more engineered, precise, and clinically defined, while many MSC developers expand into MSC-EV solutions and fuel excitement around both modalities.

MSC-EVs: Increasing Interest in a Novel Therapeutic Solution

The shift of MSC-EVs from “cells as drugs” to “cells as biological triggers” raises an interesting central question: can developers deliver therapeutic impact without administering the cells themselves?

With more than 500 MSC-derived EV clinical trials underway, the field continues to grow. MSC-EVs lead the EV and exosome space because of the strong foundation built during decades of MSC research. However, key questions remain around classification, safety, efficacy, scale-up, and commercialization. MSC-EVs remain in a regulatory grey zone, with agencies still determining whether they are biologics, cell-based therapies, or a new class. Regulators are likely to focus on process consistency, EV identity, and release testing in later-stage development.

Purity and characterization remain central because upstream and downstream processes can change EV composition. Each indication must show how cell source, processing, and purification affect the final product. With no commercial EV therapeutics approved so far, developers must establish precedent while maintaining consistency through scale-up. As MSC-EV developers scale into larger trials and commercial manufacturing, GMP processes and reagents can change EV outputs and must be addressed early. Early conversion to GMP media and consumables can reduce risk, lower costs, and clarify efficacy, purity, and consistency priorities. MSC-EVs will also face competition from EVs derived from NK cells, macrophages, HEK293 cells, plants, and other sources. These alternatives may offer lower-cost production or different applications, while shared learnings can advance the broader EV field.

MSCs and MSC-EVs Drive Progress and Advance Regenerative Medicine

Immunotherapies have defined a recent Golden Age in cell and gene therapy. As manufacturing matures and refinements become more incremental, the next major wave of innovation may come from regenerative medicine. MSCs and MSC-EVs hold major promise, but many companies still lack the infrastructure and timelines that attract major pharma investment. This places the field in a biotech Bronze Age: rich with opportunity in rare disease, organ failure, allogeneic therapies, and scalable EV platforms, but still building the evidence, biology, and manufacturing precedent needed for broader success. Continued progress in scale-up, process control, and modality definition could unlock a future Golden Age for MSC and MSC-EV therapeutics.

Jessica Pickrell; Associate Director, Media Solutions, Lonza

Further Reading

1. Wang CK, Tsai TH, Lee CH. Regulation of exosomes as biologic medicines: Regulatory challenges faced in exosome development and manufacturing processes. Clin Transl Sci. 2024; Aug 17(8):e13904. doi: 10.1111/cts.13904. PMID: 39115257; PMCID: PMC11307316.

2. Bourcier AJ & Kirkor ZM. Regulatory, ethical, and clinical barriers to exosome use in interventional pain medicine. Intl Pain Medicine 2026; 5(1):100746. doi: 10.1016/j.inpm.2026.100746.

3. nternational Society for Cell & Gene Therapy (ISCT). 2026. Roundtable on Regulation and Policy, ISCT 2026 Annual Meeting, Dublin, Ireland.

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Research lead Darrell Green, PhD, at UEA’s Norwich Medical School, said, “We have uncovered an entirely new way of tackling the disease. We found that a drug originally developed to stop cancer could help millions of women facing the twin challenge of fragile bones and midlife weight gain. We hope our work could lead to a new generation of osteoporosis treatments that tackle bone loss while also addressing some of the wider metabolic consequences of menopause.”

Green is senior and co-corresponding author of the team’s report in npj Drug Discovery, titled “RUNX2 inhibitor CADD522 improves bone microarchitecture and lipid metabolism in post-menopausal bone loss.” In their paper the team concluded that their collective studies “… identify RUNX2 inhibition as a therapeutic strategy that simultaneously improves skeletal integrity and metabolic homeostasis, supporting further development of CADD522 for osteoporosis and other RUNX2-driven diseases.”

Osteoporosis is a metabolic bone disorder characterized by low bone mass, structural deterioration and increased fracture risk. The disorder affects one in three women and one in five men aged over 50 years globally, the authors wrote, but there are limited therapeutic options. “… existing antiresorptive and anabolic therapies remain limited by safety concerns, contraindications and poor long-term adherence,” the authors stated. “Thus, new treatments with few side effects and broader applicability remain a clinical priority.”

Green said: “Osteoporosis affects around one in three women over the age of 50, leaving sufferers vulnerable to painful fractures that can seriously impact quality of life. Current treatments exist, but many are plagued by side effects, safety concerns or inconvenient dosing schedules that make long-term use difficult.

The researchers had previously evaluated the small molecule RUNX2 antagonist CADD522 in several preclinical cancer models. “RUNX2 is critical for in utero skeletogenesis and cancer metastasis,” they explained. Unexpectedly, studies indicated that CADD522 reduced cancer-induced bone disease, “… suggesting potential utility in osteoporosis.”

For their newly reported study Green and colleagues investigated whether RUNX2 inhibition could protect against post-menopausal bone loss, in an ovariectomy-induced mouse model, to mimic the hormonal changes seen after menopause.

The team found that animals treated using CADD522 for eight weeks showed significant improvements in bone health. Scans revealed increased bone volume and better preservation of the delicate honeycomb-like structures inside bones that are crucial for strength and resilience. Blood tests suggested the drug stimulated new bone growth, without interfering with the body’s normal process of breaking down and rebuilding bone.

Green said: “This is particularly important because many existing osteoporosis drugs work by suppressing bone loss, which can sometimes lead to complications when used for long periods.”

The biggest surprise came when the investigators looked beyond bone health, Green continued. “The mice receiving CADD522 weighed less than their untreated counterparts despite eating the same amount of food. They also had less body fat and fewer fat deposits accumulating inside their bone marrow—a process that is commonly seen after menopause and is linked to declining bone health.” The authors wrote in summary, “A remarkable finding was that the skeletal improvements occurred alongside reduced peripheral and marrow adiposity and selective remodeling of lipid metabolism.”

The team also examined brain tissue and found the drug appeared to reverse several menopause-related changes in fatty acids. Levels of beneficial omega-3 fats, including DHA, remained largely intact, while a number of other lipid abnormalities shifted back towards healthier patterns. “Rather than inducing indiscriminate metabolic disruption, RUNX2 inhibition therefore appears to restore specific lipid pathways perturbed by menopause,” the team noted. “Although the relationship between altered brain lipid composition and cognitive function was not examined in the present study, the selective remodeling of brain lipids following CADD522 treatment raises the possibility that RUNX2 inhibition may influence neurological adaptations to menopause in addition to preserving skeletal integrity.”

Green added: “We didn’t directly test for memory or thinking ability, but our work raises questions about whether this drug could one day help address wider menopause-related health problems.” The team suggests that further studies should determine whether the metabolic effects demonstrated translate into improvements in cognition or other measures of brain health.

The prospects for future clinical applications also received a boost from safety testing. Experiments in mice, rats and dogs found CADD522 could be taken orally and was well tolerated. “Cross-species pharmacokinetic and toxicological studies demonstrated oral bioavailability, favorable short-term tolerability and target engagement despite rapid systemic clearance, while cellular thermal shift assays confirmed direct engagement of RUNX2,” they noted.

The team also found the drug appeared to be metabolized more slowly in human tissue than in rodents, potentially improving its performance in people. “This is still in the early stages and has so far only been tested in animals but we hope that the benefits will translate to humans to ultimately reduce fracture rates,” added Green.

In conclusion, the authors wrote, “In summary, our findings reveal an unexpected role for RUNX2 inhibition in protecting against post-menopausal bone loss while simultaneously improving systemic metabolic homeostasis.” They suggest that their study “… establishes a translational framework for further development of CADD522 and identifies RUNX2 as a therapeutically tractable regulator of skeletal and metabolic adaptation in adulthood.”

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ProBioGen officials describe the cell line as a stable proliferating avian cell line derived from primary cells of a duck embryo. It was developed as an alternative to the use of chicken eggs for large-scale vaccine production. The cell line is available as both a suspension and adherent cell line and has been optimized for viral vaccine production and stability.

The product, which grows in a commercially available, chemically defined medium without animal components and serves as a host for a variety of different virus strains, is aimed at cost-effective production and increased manufacturing productivity.

“This additional license reflects our confidence in the technology to prepare for future clinical needs at scale,” said Alessandro Rive, chairman and CEO of Transgene.

“We value Transgene’s continued confidence in our AGE1.CR.pIX platform,” added Volker Sandig, PhD, CSO at ProBioGen. “A continuous cell line qualified as a GMP master cell bank, grown in chemically defined and animal-component-free medium, means every batch begins from the same fully characterized starting material.”

Transgene focuses on designing and developing targeted immunotherapies for the treatment of cancer. The company’s clinical-stage programs consist of a portfolio of viral vector-based immunotherapeutics. TG4050, the first individualized therapeutic vaccine based on the myvac^® platform is Transgene’s lead asset in the adjuvant treatment of head and neck cancers.