Dyno Therapeutics Launches Dyno-yp2, a Top-Performing TfR1-Mediated AAV Capsid, to Further Diversify CNS Delivery Portfolio

• New Dyno-yp2 capsid achieves both exceptional brain transduction and significant liver detargeting in TfR-humanized mice

• Dyno-yp2 expands Dyno’s optimized AAV vector suite across multiple blood-brain barrier-crossing mechanisms, enabling strategic delivery agility for therapeutic developers

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, today announced Dyno-yp2, a novel adeno-associated virus (AAV) gene delivery vector that, based on in vivo performance data, sets a new benchmark for efficient and selective central nervous system (CNS) delivery by binding the human transferrin receptor (hTfR1) to cross the blood-brain barrier (BBB) in TfR-humanized mice. Under the conditions tested, Dyno-yp2 achieved both exceptional neuronal transduction and significant liver detargeting, addressing key safety and efficacy challenges that have held back systemically delivered CNS gene therapies.

Gene therapy holds extraordinary promise for neurological diseases, but reliable and translatable delivery to the CNS remains challenging, which results in high costs and complexity of developing new transformative medicines. A handful of biological transport mechanisms have demonstrated the potential to deliver AAV capsids across the BBB, but no single approach has emerged as a universal solution. As a result, CNS delivery continues to be an area where innovation is essential to overcome translational uncertainties.

Dyno is uniquely positioned to help gene therapy developer partners overcome these challenges. Relying on any single biological pathway can potentially tie an effective therapeutic payload to a suboptimal delivery strategy. To mitigate translational uncertainties, Dyno engineers capsids for high-potential BBB-crossing mechanisms and provides developers access to multiple capsids with distinct mechanisms, creating strategic delivery agility for developers as the optimal CNS delivery route becomes clear in coming years. Dyno’s novel generative AI models, trained on billions of in vivo measurements, most recently accelerated with NVIDIA hardware and software, using Hopper GPUs on DGX Cloud and libraries such as TransformerEngine, integrate sequence- and structure-based approaches to engineer functional capsids for new and promising BBB-crossing mechanisms with exceptional efficiency. Dyno-yp2 exemplifies this strategy, demonstrating what's possible when a validated biological pathway is paired with state-of-the-art AI-driven capsid engineering.

In vivo studies in TfR-humanized mice showed that Dyno-yp2 achieved greater than 94% neuronal transduction following systemic administration and an 11-fold improvement in brain biodistribution (as measured by vector genomes per diploid genome), compared to the BI-hTFR1 capsid, a leading published comparator. Dyno-yp2 also demonstrated significant liver detargeting, by 80-fold compared to BI-hTFR1 and 29-fold compared to AAV9. These data highlight Dyno-yp2’s combination of potent CNS transduction with minimized off-target exposure.

“Based on early signals in our data, we identified TfR1-mediated transport as a high-potential mechanism in 2024 and moved quickly to explore it with our platform and compare performance head-to-head against BI-hTFR1 in our in vivo studies,” said Adrian Veres, Ph.D., Chief Scientific Officer and Cofounder of Dyno Therapeutics. “Dyno-yp2 is the result of just a few months of focused design, build, and test cycles. The speed at which we were able to go from hypothesis to high-performance capsid highlights the power of our AI-driven platform and the depth of our in vivo datasets.”

Dyno-yp2 is available for licensing directly and to support demonstrating the effectiveness of innovative therapeutic payloads through Dyno’s Frontiers Program, enabling gene therapy developers to rapidly evaluate and advance CNS-targeted payloads using Dyno’s leading delivery technology. Dyno-yp2 has already been onboarded at Trisk Bio, a Dyno Frontiers Manufacturing Partner with deep experience manufacturing Dyno capsids.

“We’re excited to add Dyno-yp2 to our growing collection of Dyno capsids available for large-scale manufacturing,” said Gaurav Venkataraman, Ph.D., CEO and Cofounder of Trisk. “As always, material we make is purified with chromatography instead of ultracentrifugation, in a fully scalable way that ensures both clinical comparability and predictability. We are ready to work with developers to move quickly into in vivo studies with confidence.”

Dyno-yp2’s CNS delivery is mediated by hTfR1, a transport pathway successfully leveraged by approved human therapies in non-AAV modalities. While hTfR1 represents one promising route across the BBB, Dyno views it as part of a broader toolkit rather than a singular solution. In parallel with its work on TfR1-mediated delivery, Dyno is advancing capsids that engage additional BBB transport pathways, including several BBB-receptors discovered by Dyno, as well as approaches involving alkaline phosphatase (ALPL), a compelling and distinct mechanism with translational relevance across species. This multi-mechanism approach demonstrates the breadth of Dyno's investment in mechanism diversity to identify the best CNS capsid and towards creating strategic delivery agility for partners developing gene therapies for debilitating neurological indications.

“The challenge of delivery and complexity of BBB-biology are obstacles that all CNS gene therapy developers must confront,” said Eric Kelsic, Ph.D., CEO and Cofounder of Dyno Therapeutics. “Partnering with Dyno in the CNS gives gene therapy developers strategic delivery agility to access capsids from multiple mechanistic classes, enabling them to be first-to-market with a best-in-class product in highly competitive CNS indications. At Dyno, we’ve built a portfolio of CNS capsids that leverage all attractive paths into the brain. Dyno-yp2 shows what’s possible when we optimize for a promising biological route like TfR1 to ensure our partners can successfully deliver their transformative CNS gene therapies.”

Dyno-yp2 joins Dyno’s growing suite of off-the-shelf AAV capsids, including the following capsids released in 2025: Dyno-bn8 (muscle), Dyno-3hv (neuromuscular), Dyno-4z2 (ocular), and Dyno-ahq (CNS). Together, these capsids reflect Dyno’s approach of combining deep biological insights with frontier AI design capabilities to overcome gene therapy’s persistent delivery challenges and empower patients with genetic agency – the ability to take action at the genetic level to improve their health. For more information regarding direct licensing or accessing Dyno capsids via the Dyno Frontiers Program, contact [e-mail].

About Dyno Therapeutics

Dyno Therapeutics is on a mission 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.