Boston — “If we want to treat and cure all disease, that will require enabling genetic agency,” said Eric Kelsic, PhD, co-founder and CEO of Dyno Therapeutics, in an interview with GEN. “AI will have a key role to make that possible by democratizing design.”
Kelsic defines genetic agency as a person’s ability to take action at the genetic level to live a healthier life. The term highlights the importance of creating therapeutic options where none exist and recognizes the advocacy efforts of patients and their families.
In support of this vision, Dyno hosted the inaugural Genetic Agency Technology Conference (GATC) in Boston, which gathered a group of researchers, technologists, and entrepreneurs to discuss the upcoming vision for genetic medicine, from preclinical development, such as AI for sequence design and gene delivery technologies, to manufacturing and regulatory pathways.
Among the speaker line-up included Sonia Vallabh, PhD, director of prion therapeutic science at the Broad Institute, Victoria Gray, the first patient treated with CRISPR gene editing therapy for sickle cell disease and patient advocate, and Terence Flotte, MD, provost, dean, and professor at UMass Chan Medical School and American Society of Gene and Cell Therapy (ASGCT) President.
Dyno, whose name is inspired by the climbing term for a powerful leap to a new hold, has maintained a mission to advance genetic medicines by giving its partners a competitive edge, according to Kelsic. The Boston-based genetic medicines company spun out of the lab of George Church, PhD, founding core faculty and synthetic biology lead at the Wyss Institute.
AI-first
Kelsic describes Dyno as one of the early “AI-first” companies founded in 2018 with a focus on AI-guided capsid engineering for gene therapy. Since that time, the company has landed partnerships with Roche, Astellas, Sarepta, and Novartis for adeno-associated vectors (AAV) across the central nervous system, skeletal and cardiac muscle, and ocular disease.
In recent years, Dyno has incorporated both structure-based and large language models into its platform to improve protein design effectiveness, in addition to AI agents to automate R&D workflows. These agents address the “last-mile” problem in generative therapeutic design by adding scientific expertise, including molecular biology, experimental design, and discovery decisions, to general-purpose tools.
At GATC, Dyno announced updates to its AI agent platform with a call to action for beta testers. Among the agents are Parser, an autonomous agent that participates in both data and decision flow from raw lab experiments into models and product discovery, and Knowledge agent, which distills information across documents and data systems into executive summaries, allowing users to oversee the full history of gene therapy products at Dyno.
Additionally, Structure agent, p0, streamlines reasoning around protein structures, receptor targets, and payload engineering. According to Kelsic, p0 serves as a stepping stone for more partnerships in design.
“In protein design, there’s a lot of routine work, such as finding the right file, loading it into structure view, and manipulating it for visualizations,” explained Kelsic. “With a simple language prompt, Dyno p0 agent automates those steps to understand information in the context of the research topic of interest.”
At GATC, Dyno also unveiled its new Dyno-bn8 AAV vector for muscle gene therapies. While high doses of gene therapy can deliver enough payload to target cells to achieve therapeutic effect, these doses also risk liver accumulation and toxicity, off-target effects, and patient safety concerns.
Dyno-bn8 delivery visualized using mCherry reporter in the diaphragm. [Dyno]In a nonhuman primate (NHP) study, Dyno-bn8 evenly transduced more than 80% of skeletal muscle at 5.2e12 vg/kg, a dose that is 25 times lower than typical muscle gene therapies. The capsid is an improvement upon the capsid’s predecessor, Dyno-3hv, for neuromuscular delivery, which was recently announced at the American Society for Gene and Cell Therapy (ASGCT) meeting held in May.
Additionally, Dyno announced a partnership with Trisk Bio for strategic manufacturing, as an expansion of the company’s Frontiers program. Originally launched in May, Frontiers enables partners to use Dyno capsids, at no cost, to test their engineered payload of interest in the NHP in vivo context. The program enables Dyno to evaluate capsids within different payload contexts, while therapeutic developers can acquire in vivo data to inform their next directions in the development pipeline.
The newly expanded program extends access to the manufacturing marketplace for all Frontier participants, eliminating the need to re-test capsids in manufacturing workflows to save time and cut costs.
From accelerating drug discovery speed to potentially bringing transformative treatments for N-of-1 diseases on demand, time will tell whether this AI-based vision for genetic agency comes to fruition.
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