Nature Biotechnology, Published online: 13 May 2026; doi:10.1038/s41587-026-03128-x
A deep-learning method predicts T cell receptor specificity and disease-associated antigens.
Immune-remodeling mRNAs expressing IRF8 or NIK generate durable antitumor immunity in multiple cancer models
Nature Biotechnology, Published online: 13 May 2026; doi:10.1038/s41587-026-03115-2
Immune-remodeling mRNAs delivered in lipid nanoparticles boost antitumor immunity.
Gene Therapy ETX101 Improves Seizures and Neurodevelopment in Dravet Syndrome in Phase I/II
Dravet syndrome has long represented one of the most challenging pediatric epilepsies encountered in neurology and genetic medicine. Caused primarily by loss‑of‑function variants in SCN1A, the disorder emerges in infancy with prolonged febrile seizures and evolves into a lifelong condition marked by treatment‑resistant epilepsy, developmental delay, and significant morbidity. As the gene and cell therapy community gathers for the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, the field’s attention is turning toward approaches capable not only of reducing seizures but also of altering the developmental trajectory that defines the disorder. This year’s Presidential Symposium features new data on ETX101, an investigational gene regulation therapy from Encoded Therapeutics, that appears to move the needle on both fronts.
Encoded Therapeutics, a clinical‑stage biotechnology company developing precision genetic medicines for severe neurological disorders, has engineered ETX101 as a one‑time AAV9‑based therapy designed to increase expression of SCN1A. Rather than replacing or editing the gene, ETX101 aims to restore physiologic sodium channel function in inhibitory interneurons. The company’s Phase I/II POLARIS program is evaluating the therapy across multiple international sites in children ranging from six months to seven years of age.
The dataset presented at the ASGCT Presidential Symposium expands the emerging clinical profile of ETX101, incorporating additional patients, early readouts from the highest dose level, and longer‑term follow‑up. Across the cohort, treatment with a single intracerebroventricular dose produced a robust and dose‑dependent antiseizure effect that persisted through 52 weeks of observation. At dose level three, children experienced a median seizure reduction of approximately 76%, a notable finding given that this developmental window is typically associated with escalating seizure burden despite standard therapies. Early data from the top dose level suggest even stronger responses in participants who did not receive sirolimus, consistent with preclinical evidence that the drug can dampen protein expression.
Beyond seizure control, the therapy appears to influence developmental domains that are rarely improved in Dravet syndrome. Children who reached one year of follow‑up demonstrated measurable gains across communication, motor function, and other adaptive behaviors, as assessed by caregiver‑reported Vineland Adaptive Behavior Scales. Particularly striking were the trajectories of children treated before age two. In this group, cognitive assessments showed early and sustained divergence from the stagnation observed in the ENVISION natural history study, with trajectories more consistent with neurotypical development over the first year after treatment.
Families and clinicians have taken note of the dual signal emerging from the POLARIS dataset. “Parents of children with Dravet syndrome live with the fear of every seizure and the heartbreak of watching development stall,” said Mary Anne Meskis, CEO of the Dravet Syndrome Foundation. “To see the early and robust seizure reductions paired with meaningful developmental gains is profoundly encouraging. Families have been waiting for therapies that don’t just manage symptoms but give their children a chance to keep learning and growing.”
Encoded’s chief medical officer, Sal Rico, MD, PhD, underscored the significance of the findings. “Watching these young children not only achieve durable seizure reduction but also show early evidence of neurodevelopmental rescue is truly remarkable,” he said. “These data reinforce our belief that ETX101 has the potential to change the course of the disease and future outlook for the Dravet community.”
ETX101 has been well tolerated across all four dose levels, with no treatment‑related serious adverse events. Transaminase elevations, a known AAV class effect, were the most common treatment‑related finding; they were asymptomatic and resolved with standard management.
As the ASGCT community continues to explore the boundaries of genetic medicine, ETX101’s early results highlight the promise of targeted gene regulation as a therapeutic modality. For a disorder like Dravet syndrome, the possibility of addressing both seizures and developmental delay marks an important moment for the field.
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STAT+: Drug meant to make gene therapy safer may also make it less effective
BOSTON — A medicine increasingly used to mitigate the risk of deadly gene therapy side effects could also blunt the therapy’s effectiveness, a new study finds.
The trial, from the startup Encoded Therapeutics, tested a gene therapy for Dravet syndrome, a severe form of genetic epilepsy. A key concern in gene therapy trials is that patients could mount an immune response against the engineered viruses used to deliver new genes into the brain.
In the study, Encoded assigned most of the 21 children in the trial to receive steroids, the most commonly used immune suppressant. A subset — including most of the patients on the highest dose level — were assigned to also receive sirolimus, also known as rapamycin, a drug historically given to prevent rejection in transplant recipients.
A plan to make drugs in orbit is going commercial
Varda Space Industries, a startup that’s been pitching its ability to perform drug experiments in space, says it has signed up the pharmaceutical company United Therapeutics in what may be remembered as a notable step toward in-orbit manufacturing.
The idea of building things in outer space for use on Earth has so far been explored mostly on board the International Space Station, and only in small-scale experiments backed by governments.
But Varda, based in El Segundo, California, is now telling drug companies it has a practical, and repeatable, way to produce novel molecules in microgravity.
“This is the first commercial path to products made in space,” says Michael Reilly, Varda’s chief strategy officer.
The scientific idea is that chemical mixtures have different properties under weightless conditions. For instance, water will hang together in a wiggly sphere, since without gravity, surface tension is the strongest force present.
The plan is to launch versions of United Therapeutics’ drugs into orbit, where they can be allowed to form solid crystals. The hope is that in microgravity, they’ll take on atomic arrangements not seen on Earth, possibly leading to new versions with improved stability or other valuable properties.
United is led by CEO Martine Rothblatt, who worked on early telecommunications satellites. Since then, she’s built a multibillion-dollar health franchise with a succession of drugs to treat a lung disease called pulmonary arterial hypertension, which her daughter suffers from, and a subsidiary developing genetically modified pigs as a source of organs for transplantation.
Rothblatt says space could be the next step if orbital conditions permit United to identify “even more amazing” versions of its drugs.
Space to reformulate
Pharmaceutical companies often try to keep their blockbuster franchises alive by creating improved versions of drugs or reformulating them—for example, making the switch from a pill to an inhaled version, as United has done with some of its products. Doing so can keep imitators at bay and create extra decades of patent protection.
Assisting drugmakers are specialist companies, such as Halozyme and MannKind, that earn profits by helping to reformulate other companies’ drugs, often taking a royalty on future sales.
That’s the business Varda has been trying to break into—by using excursions into space instead of nebulizers, patches, or nanoparticles. The company was formed in 2021 by Delian Asparouhov, a partner at Peter Thiel’s Founders Fund, along with Will Bruey, a former avionics engineer with Elon Musk’s SpaceX who is now the company’s CEO.
The pair’s bet is that space manufacturing will become viable once rocket launches become frequent enough—and cheap enough—to support a business model in which raw materials are sent into orbit, processed, and then returned to Earth in a new form.
And that’s starting to happen. To get into space, Varda has been purchasing rides from SpaceX—which now launches a rocket every two or three days, usually a reusable Falcon 9.
Those rockets have a nose cone, or payload fairing, about the size of a moving truck that gets filled with satellites or instruments, which are then released into orbit.
Starting in 2023, Varda began sending up small satellites that have a boulder-size capsule attached. The capsule contains equipment to carry out experiments, and it can detach and fall back to Earth, entering the atmosphere at a speed of around Mach 25 before slowing via air resistance and eventually drifting to land with a parachute. (Varda lands its craft in the Australian outback.)
That speedy reentry has also drawn interest from the US military, including the Air Force, which has paid Varda to fly instruments and take measurements relevant to hypersonic missile technology. Of the six craft Varda has paid to put into orbit so far, half have been dedicated to military research and half carried drug-related demonstrations.
At Varda, such “dual use” of technology is accepted as part of being in the space business, which remains reliant on government support. The company’s founders say Varda may be the only company that employs hypersonic engineers and pharmaceutical chemists under the same roof.
COURTESY VARDA
Launching industries
Actual space manufacturing still remains mostly an aspirational project. In 2021, Jeff Bezos, after his first trip aloft in a rocket, suggested that polluting industries should be moved beyond the atmosphere. “We need to take all heavy industry, all polluting industry, and move it into space. And keep Earth as this beautiful gem of a planet that it is,” he told MSNBC.
Weight is the big obstacle to such dreams. It still costs around $7,000 to launch a single kilogram of payload into orbit, which makes it impractical to, say, send cotton into space to be dyed there, or even to launch the acids and solvents needed to make a semiconductor chip.
But drugs may be among the few exceptions to this economic rule, since pound for pound, they can be as valuable as rare radioactive isotopes and fine-cut diamonds.
For instance, just one kilogram of the weight-loss drug Ozempic is worth more than $100 million at retail. (The reason your Ozempic bill is only $1,000 a month is that minute quantities of the active ingredient are present in the shots.)
That’s why Varda thinks it may eventually be able to manufacture drugs in orbit. However, its effort with United is more of a flying experiment to learn whether the company’s lung medicines will crystallize differently in microgravity.
The terms of the deal between Varda and United aren’t public, and the companies haven’t said which specific drugs the collaboration will study. But Rothblatt did confirm that United is paying Varda to help it identify new crystal forms of its drugs (also called polymorphs), which it hopes could have improved properties.
“One has to do the experiment to find out if that is so. The first part of the experiment is to see what polymorphs of these molecules can be made without the influence of gravity,” she says. “Then, once we have those polymorphs, we will test them.”
There is good evidence that crystals form differently in space. For instance, in 2017 the pharmaceutical giant Merck sent samples of its cancer immunotherapy drug Keytruda to the International Space Station, where it was found to form crystals of a single size. On Earth, the drug tended to form two different sizes at once.
That experiment offered clues for how to formulate the drug as a shot instead of administering it intravenously. Still, when Merck introduced a Keytruda injection last year, it ended up using a different approach. That means there’s still no straight-line connection between orbital discoveries and any drug here on Earth. Actual space factories are another step further from reality.
“We’ve been learning from space for years, but I can’t name anything manufactured in space, brought down to Earth, and sold,” says Reilly. “So that is a first—or it will be a first.”
Reilly says that Varda anticipates launching United Therapeutics’ drugs into orbit sometime early next year.
AAVs in Focus: Practical Approaches to Capsid Analytics and Plasmid DNA Control
Adeno-associated viruses (AAVs) continue to be a foundational platform for gene therapies, with rapid advances in vector design, analytics, and manufacturing practices. This three-part USP webinar series on AAV guides participants through a progressive learning journey starting with the current AAV landscape, then advancing to focused, practical discussions on capsid characterization, and ending with specialized session focused plasmid DNA starting materials.
Throughout this series, experts from USP and industry will share first-hand experiences, case studies, and practical insights on how AAV analytics and material controls are evolving. This series will identify common AAV challenges and explore effective solutions across different stages of development.
Why Attend the AAV Webinar Series?
- Broaden attendees’ understanding of the current AAV landscape by learning from experts about key scientific, analytical, and manufacturing considerations
- Learn how developers approach capsid characterization, full/empty analysis, and data comparability, and how production and analytical teams work together to optimize AAV manufacturing
- Discover more about the critical role of plasmid DNA as a starting material, and how expectations change from early development to later stages
- Engage directly with subject matter experts during live Q&A sessions
May 19, 2026
June 16, 2026
July 8, 2026
AAV Manufacturing: Best Practices in Quality Control and the Role of USP Standards
Practical Strategies for AAV Capsid Characterization
Characterizing Plasmid DNA to Improve AAV Manufacturing
A live Q&A session will follow the presentation, offering you a chance to pose questions to our expert panelists.
Produced with support from:
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Stable Producer Cell Line Generation Platform Adds to VIVEbiotech’s Lentiviral Vector Manufacturing Capabilities
VIVEbiotech, a Spanish lentiviral vector (LVV) CDMO, has added EvoLVcell to its catalog of LVV-manufacturing products. EvoLVcell is a stable producer cell line (SCL) generation platform designed to reduce batch‑to‑batch variability, improve vector quality, and provide a more predictable long‑term production strategy for LVVs. The fully integrated platform requires only the addition of a developer’s transgenic element to the fully characterized monoclonal PCL, avoiding transfection, explained a VIVEbiotech spokesperson, who added that this simplifies the manufacturing workflow, improving long-term predictability and reducing reliance on plasmid and transfection reagent supply chains.
The characterized, inducible, monoclonal lentiviral packaging cell line (PCL) derisks SCL generation by incorporating the therapeutic transgene that typically would be transfected together with the helper plasmids, noted Andrés Lamsfus-Calle, PhD, product development manager at VIVEbiotech. This SCL platform generation enables VIVEbiotech to get a prototype cell line in three months, pointed out Lamsfus-Calle.
EvoLVcell reduces variability and produces fewer impurities, of particular importance to gene therapeutics, according to a company statement. “At the same time, the platform’s extensive characterization enables rapid yield assessment through a rapid proof-of-concept, allowing developers to reach a clear go/no-go inflection point in just three months,” continued the statement.
“Achieving cost efficiency and high reproducibility is essential for the scalable production of lentiviral vectors and for expanding patient access. Stable producer cell lines provide a reliable and scalable manufacturing platform to support this goal,” said Lamsfus-Calle.
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How HIV-1 Develops Resistance to Broadly Neutralizing Antibodies
One of the most challenging aspects of combatting HIV-1 infection is that the virus continually evades neutralizing antibodies. However, one consequence of this is that a small percentage of people with HIV-1 (1-5%) develop rare, broadly neutralizing antibodies (bNAbs) that can neutralize a large fraction of global HIV-1 isolates. These broadly neutralizing antibodies are among the most promising new long-acting HIV treatments, offering the potential to forego traditional daily dose of antiretroviral drugs. Indeed, a recent trial found that participants who received a single dose of two bNAbs maintained a nearly undetectable viral load for up to 20 weeks, and a third did so for about a year.
Despite the known promise of bNAbs, the pathways through which the virus escapes these antibodies remain incompletely understood across diverse HIV-1 strains.
“Knowing how different strains of the virus respond to leading bNAb therapies will greatly improve our ability to anticipate whether a particular therapy will be effective for individual patients,” says Paul Bieniasz, PhD, professor at The Rockefeller University and an HHMI Investigator. “And if we can identify broadly neutralizing antibodies that the majority of strains have great difficulty escaping from, we can create more robust treatments.”
Now scientists have established the most comprehensive view to date of how HIV-1 can escape bNAbs. Using thousands of parallel viral selection experiments combined with bioinformatic analysis and experimental validation, the team discovered viral mutations that make HIV-1 strains resistant to two bNAbs: 3BNC117 and 10-1074.
This work is published in Nature Microbiology in the paper, “Diverse paths to broadly neutralizing antibody escape among HIV-1 strains.“
The researchers sought to investigate the relationship between different HIV-1 strains and bNAbs collected from HIV infected persons. Only a handful of resistance mutations have been identified in a limited number of viral strains. The researchers wanted to expand that number to represent global viral diversity.
“No one has attempted to do this at such a scale before,” said Theodora Hatziioannou, PhD, research professor at The Rockefeller University.
The team developed an approach that would allow them to study the mutational pathways to escape among 15 strains of HIV-1 sourced from around the globe. The goal was to pinpoint the mutations that were contributing to each strain’s propensity to develop resistance.
“We found that most viral strains can escape bNAb neutralization, but there’s substantial variation in the likelihood that they will and the mechanisms that enable it,” says Alex Stabell, MD, PhD, an infectious disease physician and clinical scholar at The Rockefeller.
Stabell devised a pipeline that began by growing large amounts of virus in cell culture. The bulk populations were used to seed thousands of parallel selection experiments with varying concentrations of bNAbs. Viruses that were able to spread in the presence of the bNAbs were isolated and sequenced. Custom bioinformatic processing gave a list of putative resistance mutations, which were subsequently experimentally validated for each viral strain.
Using this method, called RISC (resistance identification via selection and cloning), the team found more than 100 bNAb escape mutations across the 15 viral strains tested, dramatically expanding the known number. Surprisingly, they found that in most cases, a single amino acid change may be enough to confer resistance. That turned out to be true for 12 of the 15 viruses tested against the 3BNC117 antibody and for all nine tested against 10-1074.
“It was striking that it’s actually quite easy for most HIV strains to escape these special antibodies,” Bienasz says. “But it’s not true for all strains—a handful Alex worked with needed multiple amino acid substitutions or unusual ways to replicate in order to escape.”
“The genetic barrier to resistance was higher for these viruses,” Stabell adds. “One of the goals of therapy these days is not simply to have therapies that are transiently effective, but to have this high genetic barrier.”
They also identified a surprising number of mutations occurring outside the epitope on the viral envelope recognized by bNabs that target the CD4 binding site, such as 3BNC117. (10-1074 aims for a more mutable envelope target, which may help explain why it’s easier to escape.) “These were quite prominent and unexpected,” says Hatziioannou. “No one would have predicted these would affect bNAb sensitivity.”
In the future, the team will use Stabell’s method to identify to discover resistance mutations to other bNAbs as well as to combinations of them.
“HIV-1 mutates so fast and the diversity in the population is already quite enormous, so we’ve long known that a multidrug approach is the best course of treatment,” Hatziioannou says. “We hope to identify combinations that potentially raise the genetic barrier to resistance and are therefore more effective.”
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Genewiz Launches Gene Synthesis 2.0
Genewiz, Azenta Life Sciences’ genomics services provider, launched Gene Synthesis 2.0, an updated platform designed to simplify how researchers design and order genes.
Built around three packages, Sprint, Flex, and Flex+, Gene Synthesis 2.0 introduces a streamlined, intuitive ordering experience, according to Trey Martin, president of Genewiz, who adds that researchers can design cloning strategies, select vectors, assess sequence complexity, and place orders in minutes.
The product also introduces an upgraded codon optimization capability that combines established heuristic approaches with machine‑learning models trained on a high‑expression dataset, continues Martin. This approach can improve expression reliability across a wide range of organisms and sequence architectures while maintaining customer control over design choices, he points out.
“Gene Synthesis 2.0 reflects how researchers work today—where speed, clarity, and reliability matter at every step,” says Martin, “By simplifying the path from sequence design to execution, this offering helps scientists move faster in rapidly evolving fields such as antibody discovery, AI-enabled biology, and gene and cell therapy.”
Gene Synthesis 2.0 is being highlighted at ASGCT this week at booth 915.
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RegVelo AI Model Predicts Cell Fate, Tackles Developmental Disorders and Cancer
In a new study published in Cell titled, “RegVelo: gene-regulatory-informed dynamics of single cells,” researchers from Stowers Institute of Medical Research have developed a new AI model that connects two areas of single-cell biology that have often remained separate: estimating how cells change over time and inferring the gene regulatory networks controlling those changes.
“You can imagine if you had a very early set of cells, having a particular set of instructions could allow you to reproduce, in vitro, some of these cell types in a very natural way. These cells could then be used in cell therapies in regenerative medicine,” said Tatjana Sauka-Spengler, PhD, Stowers Institute Investigator and co-senior author of the study.
While development is often described as a series of static snapshots of cell states, RegVelo models how these fate decisions are encoded in gene regulatory networks over time and space, and what drives cell state transitions. In zebrafish neural crest development, RegVelo identified an early driver of pigment cell formation (tfec) and revealed a previously unknown regulator of pigment cell fate (elf1). The neural crest is a developmental system that gives rise to many different cell types, including pigment cells, craniofacial tissues, and parts of the peripheral nervous system.
CRISPR/Cas9-mediated knockout and single-cell Perturb-seq supported predictions, showing that the model could do more than describe developmental changes and generate biologically meaningful hypotheses that held up in living systems.
Alejandro Sánchez Alvarado, PhD, Stowers President and chief scientific officer says RegVelo’s value “extends well beyond” neural crest cells and is applicable to any system in which cells change over time, from basic developmental biology to modeling tumor trajectories and the cellular outcomes that may inform treatment.
“Sauka-Spengler and her collaborators have developed a meaningfully different way to process this kind of data,” said Sánchez Alvarado. “It allows us to infer the most likely path of each component through space and time, and to use deep learning to predict those dynamics and test them experimentally.”
Single-cell biology research has made it possible to build increasingly detailed maps of development. RNA velocity methods can help researchers estimate how cells move through developmental landscapes, while gene regulatory network approaches can identify relationships among genes. However, these methods have typically been used in parallel rather than together.
“For a long time, cellular dynamics and gene regulation have largely been modeled separately,” said Fabian Theis, PhD, the study’s co-senior author and director of the institute of computational biology at Helmholtz Munich. “RegVelo brings those pieces together, allowing us to ask not only how cells are changing, but which regulatory interactions are helping drive those changes.”
The framework jointly models splicing kinetics and gene regulatory relationships, allowing researchers to map the hidden timeline of cell development, predict how cells shift from one state to another, and test what might happen when specific regulators are perturbed.
The framework can incorporate additional regulatory layers, including chromatin, protein activity, and other multimodal measurements. While the study’s limitations include simplifying assumptions around latent time, regulatory interactions, and computational cost, the results demonstrate a compelling proof of principle.
“When dynamic cell-state modeling is linked directly to gene regulation, it becomes possible to move closer to mechanism and then discovery,” Sauka-Spengler said.
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