Dyno Therapeutics, a biotechnology company that emerged from the laboratories of Harvard University, is focused on advancing the field of gene therapy. The company was founded to address a major bottleneck in gene therapy: engineering improved delivery vehicles to effectively transport therapeutic genes to target cells. This enables gene therapies to become more potent, safe, and broadly applicable to a wider range of diseases. By pioneering new technologies, Dyno aims to overcome existing biological barriers that have limited the success of many promising genetic medicines.
The Challenge with Gene Therapy Vectors
Gene therapy holds the promise of treating diseases at their genetic root, often by delivering a functional copy of a faulty gene into a patient’s cells. This delivery is accomplished using a vector, which acts as a transport mechanism. The most commonly used vectors today are derived from the adeno-associated virus (AAV), a small, non-disease-causing virus that can effectively carry genetic material into human cells. AAVs are favored for their strong safety profile and their ability to be engineered to carry therapeutic payloads instead of their own viral genes.
Despite their utility, naturally occurring AAVs present significant challenges. A major hurdle is pre-existing immunity; a large portion of the human population has antibodies that can neutralize the vector before it reaches its target, rendering the therapy ineffective. These natural viruses were not evolved for therapeutic purposes and lack optimal features for medical use.
Another limitation is their lack of tissue specificity. An ideal gene therapy vector would travel directly to the intended cells, but natural AAVs often lack this precise targeting ability. This can lead to lower efficacy and potential side effects if the therapeutic gene is delivered to the wrong location. Inefficiencies in the manufacturing process and the quantity of vector required also complicate their use.
Dyno’s AI-Powered Solution
To overcome the limitations of natural viruses, Dyno Therapeutics developed a proprietary technology platform called CapsidMap™. This platform integrates machine learning, high-throughput DNA sequencing, and extensive in vivo experiments in animal models to systematically design and optimize AAV capsids. The capsid is the protein shell of the virus that determines its physical properties, including which cells it can enter and how it interacts with the immune system.
The process begins by creating immense libraries of AAV variants, each with small, programmed changes to its capsid proteins. These variants are then tested in living organisms to measure their performance, such as their ability to reach specific tissues or evade the immune system. The resulting data, which details how millions of different capsid designs behave, is fed into machine learning algorithms. This approach allows the company to understand the complex rules governing capsid biology.
Armed with this predictive understanding, Dyno can computationally design entirely new, synthetic AAV capsids. The goal is to create vectors tailored for therapeutic use, featuring enhanced targeting, a reduced susceptibility to pre-existing antibodies, and improved manufacturing characteristics.
Strategic Partnerships and Collaborations
The potential of Dyno’s CapsidMap™ platform has attracted significant interest from major players in the pharmaceutical and biotechnology industries. These collaborations provide the resources to apply it to pressing medical needs. Partnering with established companies allows Dyno to accelerate the development of its custom-designed vectors for specific diseases by leveraging the clinical expertise of its partners.
Dyno has entered into several partnerships to develop next-generation AAV therapies. For instance, a collaboration with Novartis focuses on creating improved vectors for ocular diseases. Another partnership with Sarepta Therapeutics is aimed at designing capsids for muscle diseases, which require systemic delivery to muscle tissue throughout the body.
Further expanding its reach, Dyno has also established collaborations with Astellas Pharma for muscle diseases and Roche for central nervous system (CNS) disorders and liver-directed therapies. These agreements involve upfront payments, research support, and potential future milestone payments and royalties, which in total could amount to billions of dollars.
Targeted Therapeutic Areas
The custom-designed AAV vectors are being developed for several therapeutic areas, including ocular diseases, disorders of the central nervous system, muscle diseases, and conditions affecting the liver. The platform’s capabilities are also being expanded to target the lung, heart, and kidney.
For each of these areas, a superior AAV vector is needed to overcome distinct biological barriers. In the treatment of CNS disorders, for example, a vector must be able to cross the blood-brain barrier. Treating systemic muscle diseases like Duchenne muscular dystrophy requires a vector that can efficiently target muscle cells throughout the body. In ophthalmology, enhanced vectors could lead to safer treatments by ensuring the therapy is confined to the eye, while improved capsids for liver-directed therapies could increase the efficiency of gene transfer.