- Non-human primate study results demonstrate improvements in skeletal and cardiac muscle delivery efficacy, safety potential, human translatability, and manufacturability over prior AAV capsids
- Breakthrough capsid, announced during Dyno’s Genetic Agency Technology Conference (GATC), is available to license for gene therapy developers and Dyno Frontiers Partners
WATERTOWN, Mass.–(BUSINESS WIRE)–Dyno Therapeutics, Inc., a genetic technologies company applying artificial intelligence (AI) to solve the grand challenge of in vivo gene delivery, announced Dyno-bn8, a novel adeno-associated virus (AAV) gene delivery vector targeting skeletal and cardiac muscle with best-in-class potential, at Dyno’s Genetic Agency Technology Conference (GATC). Demonstrated in non-human primate (NHP) study results, Dyno-bn8’s highly-engineered muscle tropism makes it possible to reach the vast majority of muscle fibers via systemic intravenous (IV) injection at an exceptionally low dose of 5.2e12 vg/kg, a 25-fold reduction compared to existing muscle gene therapies dosed at 1.33e14 vg/kg. Dyno-bn8 delivery has the potential both to lower manufacturing costs of a curative gene therapy dose and to improve the safety through a combination of lower doses and Dyno-bn8’s engineered liver detargeting.
Inefficient gene delivery limits the development of curative gene therapies for muscle and neuromuscular diseases. Current AAV vectors require injection of high doses to reach therapeutic levels of delivery and preferentially accumulate in the liver, which at times can cause toxicity through damage to the liver or from immunological responses to the gene therapy. To solve these problems, Dyno scientists trained AI sequence design models using proprietary NHP performance data for millions of capsids and applied them to create Dyno-bn8, a novel AAV capsid with broad tropism to muscle cells, substantial liver detargeting and straightforward manufacturability.
“For 10 years, we’ve been working day and night to achieve therapeutic delivery to both skeletal and cardiac muscle at low doses while dramatically reducing off-target liver exposure. Dyno-bn8 now leads the field for muscle delivery. We’re excited about what this enables for Dyno’s partners and for gene therapy patients,” said Eric Kelsic, Ph.D., CEO and Cofounder of Dyno Therapeutics. “By solving the grand challenges that have kept genetic medicines out of reach for so many, Dyno is becoming the partner of choice for developers of breakthrough genetic medicines.”
Administered systemically in NHPs at a dose of 5.2e12 vg/kg, the capsid transduced 81% of target skeletal muscle cells and 20% of cardiac cells throughout the body. Dyno-bn8 outperformed a previously published capsid, MyoAAV-4E (Tabebordbar et al., 2021), in a head-to-head comparison of muscle tropism and liver detargeting. These findings provide compelling evidence of Dyno-bn8’s efficient, best-in-class delivery and improved safety potential over existing muscle-targeted capsids.
Dyno also reported key findings that underscore Dyno-bn8’s readiness for the clinic. The company identified a highly conserved receptor that confers enhanced muscle tropism and demonstrated that Dyno-bn8 interacts with both NHP and human orthologs. Dyno-bn8’s enhanced muscle tropism is also recapitulated with in vitro experiments using human muscle cell lines. Finally, Dyno-bn8 is easily manufactured at a large scale and is compatible with existing AAV9-based processes, streamlining and de-risking the production process, a frequent cause of uncertainty and delay for gene therapy developers.
Dyno-bn8 is the latest in Dyno’s growing portfolio of AAV capsids, which also includes Dyno-3hv (for neuromuscular delivery), Dyno-4z2 (for ocular delivery), and Dyno-ahq (for central nervous system delivery). These off-the-shelf AAV gene delivery solutions are available for therapeutic developers to license and to apply for the demonstration of novel payload strategies through the Dyno Frontiers Program. For more information, please reach out to [email protected].
About Dyno Therapeutics
Dyno Therapeutics’ mission is to build high-performance genetic technologies that transform patients’ lives. Dyno applies AI to create better technologies for gene delivery and sequence design to increase “Genetic Agency” — a person’s ability to take action at the genetic level to live a healthier life — through safe, effective and widely accessible genetic treatments. With frontier AI models and high-throughput in vivo experimentation, Dyno designs optimized AAV delivery vectors that solve gene delivery challenges across a wide range of therapeutic applications including eye, muscle and CNS. Dyno partners across industries to ensure these life-transforming technologies can help as many patients as possible, including through strategic collaborations with leading gene therapy developers Astellas and Roche, and with technology companies including NVIDIA. Visit www.dynotx.com for more information.
Contacts
Media Contact:
Thermal for Dyno Therapeutics
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