WATERTOWN, Mass.--(BUSINESS WIRE)--Dyno Therapeutics, Inc., a techbio company pioneering applications of artificial intelligence to engineer AAV capsids that can expand the potential of genetic medicine, today announced the launch of its Dyno bCap 1™ capsid product, a breakthrough CNS-targeted AAV gene delivery vector with best-in-class potential, in a keynote address at the company’s Scientific Symposium at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting. The Dyno bCap 1 vector provides dramatically improved CNS delivery and liver detargeting compared to leading natural capsids and stronger all-around characteristics relative to other engineered CNS-IV capsids.
“Safe and effective gene delivery to the brain is a primary factor limiting the treatment of CNS diseases with gene therapy today. We believe effective delivery to all cells throughout the brain will unlock the potential to treat patients affected by a variety of genetic diseases, including amyotrophic lateral sclerosis, Angelman syndrome, Parkinson’s disease and Alzheimer’s disease,” said Adrian Veres, M.D., Ph.D., CSO and Co-founder of Dyno. “We look forward to further exploring the transformative potential of Dyno bCap 1, as well as our growing line of capsid products, by partnering with leading developers of gene therapies.”
To create high-performing capsids, Dyno has pioneered the application of state-of-the-art methods in deep learning and generative artificial intelligence (AI) to protein sequence design, while also leveraging large, internally collected in vivo datasets that provide high-resolution insights into the many therapeutically relevant capsid delivery properties. By combining AI and high-throughput biology, Dyno’s platform is capable of more fully exploring the AAV capsid sequence space in search of capsids that are optimized across multiple dimensions, such as CNS targeting, liver detargeting, and production efficiency. As a result, the protein sequence for the Dyno bCap 1 product is highly novel, with a pattern of sequence changes that would not occur using methods most typically used for engineering AAV capsids, such as random mutation or insertion of short peptides in the capsid protein sequence. After AI-driven design of the capsid sequence, Dyno extensively characterized the in vivo delivery properties of Dyno bCap 1 across species in NHPs, the most relevant animal models for translation to humans.
Key Data on Dyno bCap 1 Technology
- Relative to the commonly used AAV9 capsid, Dyno bCap1 exhibits 100-fold better pan-brain CNS transduction upon crossing of the blood-brain barrier and 10-fold better liver detargeting.
- Dyno bCap1 improvements in transduction and targeting specificity are conserved across NHP species in both cynomolgus monkey (Macaca fascicularis) and African green monkey (Chlorocebus sabaeus), increasing confidence that the breakthrough CNS delivery capabilities of Dyno bCap 1 could be relevant for applications in human therapeutics.
- Whereas naturally-derived capsids such as AAV9 transduce only a small fraction of brain cells in NHPs, with a low IV injected dose of 1e13vg/kg, payloads delivered by the Dyno bCap 1 capsid transduced between 4-14% of cells in the brain, and 5-20% of neurons across pan-brain regions and the spinal cord, potentially broadening the diseases which can be successfully treated with gene therapy.
- Compared in library format head-to-head against an external engineered AAV capsid reported to have improved brain transduction relative to other CNS-IV capsids, Dyno bCap 1 demonstrated consistent brain transduction across animals, with comparable or improved transduction relative to the external capsid, and dramatically better production efficiency, demonstrating the transformative potential of Dyno bCap 1 for CNS-IV delivery.
Licensing Dyno bCap 1 Technology
Dyno Therapeutics is making Dyno bCap 1 technology and additional proprietary capsids with improved CNS delivery properties available immediately for licensing to gene therapy developers across academia and industry.
“Dyno’s business is partnership-centric: We partner with gene therapy developers, providing them with the very best capsids so that they can invest their efforts at the leading edge of genetic medicine,” said Dyno CEO and Co-founder, Eric Kelsic, Ph.D. “With the Dyno bCap1 launch, we are delivering on this promise for our partners, both existing and to come. We’re ready to build new partnering relationships in the CNS and beyond that will enable our industry to realize the potential of genetic medicines to help patients in need all around the world.”
About Dyno Therapeutics
Dyno Therapeutics is solving the in vivo gene delivery challenge while broadly partnering with gene therapy developers towards maximizing patient impact. Dyno’s platform combines AI with high-throughput experimentation to accelerate the design of AAV capsids with properties that significantly outperform current in vivo gene delivery vectors, with the goal of expanding the range of diseases treatable with genetic medicines. Dyno has partnered with leading gene therapy developers, including Astellas, Novartis, Roche, and Sarepta, and is broadly open to partnering across therapeutic areas. Dyno was founded in 2018 and is located in Watertown, Massachusetts. Visit www.dynotx.com for additional information.