Dyno Therapeutics has unveiled three new adeno-associated virus (AAV) capsid vectors with breakthrough potential for gene therapy delivery to the eye, muscle, and central nervous system (CNS). The company presented key data at the 28th American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, demonstrating significant improvements in delivery efficiency, target specificity, and manufacturability compared to commonly used AAV vectors.
The Massachusetts-based genetic technologies company applies artificial intelligence to address what many consider the grand challenge of in vivo gene delivery. By designing optimized capsids that more effectively transport therapeutic genetic material to specific tissues, Dyno aims to overcome one of the most significant barriers to effective gene therapy.
"I'm excited for Dyno to expand our offerings for our gene delivery partners with these new optimized capsids that more efficiently and more specifically deliver therapeutic genes to the eye, muscle and brain," said Eric Kelsic, Ph.D., CEO and Cofounder of Dyno. "These new capsids advance the frontiers of gene delivery, bringing Dyno's partners and the field one key step closer to realizing the full potential of genetic medicine to transform patient lives."
Enhanced Ocular Delivery with Dyno-4z2
The Dyno-4z2 capsid demonstrates exceptional performance for retinal delivery via intravitreal (IVT) injection, particularly for bipolar cells in the inner nuclear layer (INL). This makes it especially promising for optogenetic ocular gene therapies targeting retinal degeneration.
In non-human primate (NHP) studies, Dyno-4z2 showed:
- Greater than 40-fold improvement in broad retinal transduction compared to AAV2 at doses of 1×10¹⁰-1×10¹¹ vg/eye
- 5-fold improvement in transduction of bipolar cells compared to reference engineered capsids
- Compatibility with less invasive IVT administration, potentially expanding patient access
- Strong manufacturability at scale using AAV2-based processes
Neuromuscular Targeting with Dyno-3hv
The Dyno-3hv capsid represents a significant advancement for neuromuscular disorders, as it efficiently targets multiple affected tissues—heart, skeletal muscle, and brain—with a single intravenous administration.
Key performance metrics include:
- Transduction of 53-90% of skeletal myofibers and multiple regions of the heart and CNS with IV injection at a dose of 4×10¹² vg/kg in NHPs
- Substantial liver detargeting, with less than 10 vg/dg observed in liver after IV dosing and minimal biodistribution to other off-target organs
- Identification of a novel receptor for crossing the blood-brain barrier (BBB) with conserved binding between NHP and human orthologs
- Compatibility with AAV9-based manufacturing processes
CNS-Focused Dyno-ahq
The Dyno-ahq capsid is optimized for widespread and efficient delivery throughout the CNS via intravenous administration. This capsid demonstrates exceptional liver detargeting while maintaining high neuronal transduction efficiency.
Notable characteristics include:
- Up to 30% neuronal transduction in NHP after crossing the BBB at a dose of 3×10¹³ vg/kg—a 280-fold increase in efficiency compared to AAV9
- More than 50-fold reduction in liver targeting compared to AAV9
- Identification of a novel BBB-crossing receptor with conserved binding between NHP and human orthologs
- Compatibility with AAV9-based manufacturing processes
Addressing the Delivery Challenge
Ineffective delivery of therapeutic genes to specific organs and cells in vivo remains the most limiting challenge for gene therapy today. Dyno's platform applies advanced AI models trained on high-throughput in vivo measurements to design optimized AAV capsids.
Each of the new capsids was validated in cynomolgus monkeys (Macaca fascicularis), considered the most relevant non-human primate model for predicting translation potential to human therapy. This approach provides strong evidence for the capsids' potential effectiveness in clinical applications.
"By solving the grand challenge of in vivo delivery with optimized capsids, our goal is to enable Dyno's partners to transform patient lives with breakthrough genetic medicines," says Kelsic. "With breakthrough new capsids like Dyno-4z2, Dyno-3hv, and Dyno-ahq, we are advancing the frontiers of delivery across therapeutic areas."
Commercial Availability and Future Directions
The three new capsids join Dyno's previously released technologies—Dyno-86m (also known as Dyno eCap™ 1) for eye delivery and Dyno-hc9 (also known as Dyno bCap™ 1) for brain delivery. All are now available for licensing to gene therapy developers.
Dyno has established strategic collaborations with leading gene therapy developers including Astellas, Roche, and Sarepta, as well as technology companies like NVIDIA. These partnerships aim to accelerate the development of next-generation gene therapies incorporating Dyno's optimized capsids.
The company's scientific symposium at ASGCT, titled "Leveling up genetic medicine with frontier AI and AAV vectors for CNS, eye, and muscle," also provided updates on Dyno's AI algorithms and strategy to rapidly advance these gene therapies into human clinical trials.
By addressing the fundamental challenge of gene delivery, Dyno Therapeutics is working to make genetic medicines safer, more effective, and more accessible to patients worldwide, potentially transforming treatment approaches for a wide range of ophthalmological, neuromuscular, and neurological disorders.
