At the JPM Healthcare Conference 2026, the Genetics Podcast recorded a special episode from the Flagship Pioneering studio, bringing together two leaders advancing fundamentally new genetic medicine platforms into the clinic.
Michelle Werner, CEO of Alltrna, and Michael Severino, CEO of Tessera Therapeutics, joined host Patrick Short to discuss what it means to take engineered tRNA and gene writing technologies from years of preclinical development into first-in-human studies, and why 2026 represents a pivotal inflection point for genetic medicine.
Despite major advances in gene therapy, gene editing, and RNA medicines, most rare genetic diseases remain untreated. With roughly 10,000 known rare genetic conditions, the one-gene, one-drug development model leaves many patient populations permanently underserved.
Both Alltrna and Tessera are pursuing platform strategies designed to scale across diseases rather than address them one at a time. Their approaches differ mechanistically, but share a common goal: making genetic medicine broader, more durable, and more clinically practical.
Alltrna is built around a simple but powerful reframing of the rare disease problem. Instead of targeting individual genes, the company targets shared mutation classes that recur across many diseases.
Alltrna engineers transfer RNAs (tRNAs) to correct nonsense mutations, specifically premature stop codons that produce truncated proteins. Rather than editing DNA or replacing genes, engineered tRNAs restore the cell’s ability to translate full-length proteins.
Because the same nonsense mutation can appear across dozens or even hundreds of different genes, a single engineered tRNA may be applicable to many diseases.
Alltrna’s lead candidate, AP003, targets the arginine-to-TGA stop mutation. In preclinical studies, the same engineered tRNA restored full-length protein across:
Critically, these effects were achieved using the same molecular payload, supporting the thesis that engineered tRNA can scale across diseases.
AP003 is delivered using lipid nanoparticles (LNP), and preclinical safety data indicate a profile consistent with LNP-based RNA therapeutics rather than tRNA-specific toxicities. This reduces uncertainty around a modality that has never before been tested in humans.
Tessera’s approach, known as gene writing, is based on mobile genetic elements, evolutionarily ancient systems that naturally insert DNA into genomes. These elements are responsible for nearly half of the human genome and represent nature’s own genome engineering toolkit.
Unlike CRISPR-based editing, Tessera’s gene writers:
This allows Tessera to make durable, one-time corrections or insertions directly in vivo.
In 2026, Tessera is advancing gene writing into first-in-human trials, including programs for alpha-1 antitrypsin deficiency (AATD), a monogenic liver and lung disease, and sickle cell disease, using in vivo editing of hematopoietic stem cells.
In preclinical models, these therapeutics demonstrated greater than 90% correction of disease alleles, a level that exceeds what is required for clinical benefit in autosomal recessive conditions.
Both leaders emphasized a critical advantage of genetic medicine: preclinical predictability. Unlike complex immunologic or inflammatory diseases, monogenic disorders have well-defined causes. When a therapy restores the correct genetic sequence or protein product in validated models, clinical translation is far more reliable.
For Tessera, correction of the human disease gene in mouse and non-human primate models provides strong confidence that the same effect will translate to patients. For Alltrna, consistent protein rescue across multiple disease contexts validates the underlying biological mechanism.
Alltrna plans to use a basket trial design, enrolling patients with different diseases who share the same nonsense mutation. This strategy, already established in oncology, could be transformative for rare disease drug development.
Basket trials enable:
This approach aligns regulatory efficiency with patient equity, expanding access without compromising rigor.
As these modalities move into the clinic, both CEOs highlighted the need for specialized trial infrastructure. Key requirements include a deep understanding of genetic mechanisms among investigators and site staff, experience managing RNA and genetic therapies, robust genetic testing and mutation identification workflows, and close collaboration with patient advocacy groups. For metabolic diseases, nutritional management and disease-specific standard-of-care expertise also remain essential to generating clean clinical data.
From an execution standpoint, these requirements have direct implications for trial feasibility and scalability. Genetic medicines depend on consistent access to genotype-confirmed patients, longitudinal follow-up, and operational workflows that can support complex therapies beyond a single indication. In practice, this places pressure on sites and health systems that were not designed to deliver genetic medicines at scale.
Importantly, these capabilities are often limited to highly specialized medical centers, which may limit enrollment and exacerbate inequities in access. Extensive collaboration between industry sponsors, healthcare systems, and policy makers will be crucial for developing infrastructure that can support wider access to life-saving genetic medicines. To learn more about barriers affecting access to cell and gene therapies today, watch our webinar with experts across policy, patient advocacy, and ethics.
Beyond liver diseases, Alltrna is exploring engineered tRNA in central nervous system disorders, such as Rett syndrome, and muscle diseases, such as Duchenne muscular dystrophy. Because tRNAs are small and do not risk overexpression, they may be uniquely suited for diseases where precise protein dosing is critical or where large genes cannot be replaced by existing gene therapies.
Tessera’s platform enables not only gene correction but also gene insertion and multiplexed editing. This is being tested for in vivo CAR T therapies, autoimmune diseases, and more complex genetic correction beyond single mutations. The ability to write multiple instructions into the genome positions gene writing as a programmable therapeutic system rather than a single-use tool.
Both leaders described JPM 2026 as a return to a more constructive and confident environment. Investor interest is rebounding, large pharma remains eager for differentiated platforms, and rare diseases continue to attract attention due to clear biology and regulatory flexibility.
Importantly, truly differentiated technologies are increasingly able to define their own trajectory, independent of broader market cycles.
For Alltrna, 2026 marks the first time engineered tRNA will be tested in humans. For Tessera, it represents the transition from preclinical promise to clinical proof of concept.
Both companies exemplify a broader shift in genetic medicine: moving beyond incremental advances toward scalable, durable, and mechanism-driven therapies that address disease at its root.
As these programs enter the clinic, the field will be watching closely. If successful, they will not only validate new modalities, but also redefine what is possible for patients who have waited decades for meaningful treatment options.
Watch the full episode below.