Science

Split Intein Mediated Protein Ligation Gene TherapyTM” overcomes AAV packaging limitations by joining protein segments together to form large functional proteins. Until now, gene therapy for diseases like Duchenne muscular dystrophy and dysferlinopathies relied on truncated versions of healthy genes. The resultant translated proteins do not adequately reduce symptoms nor provide relief for patients. SIMPLI-GT can produce larger or full-length proteins to more adequately address symptoms, and potentially eliminate disease progression.

Successful gene therapy requires achieving optimal levels of therapeutic proteins. This is necessary because different NMDs affect different anatomical muscles and fiber types, and because the normal concentrations of different muscle proteins span more than a thousand-fold range. Our proprietary library of muscle-specific expression cassettes (MyoXpress™) enables optimal tuning of therapeutic protein production in skeletal and cardiac muscles while minimizing expression in non-muscle tissues.

Kinea’s proprietary myotropic capsids are engineered adeno-associated viral vectors (AAVs) formulated for neuromuscular diseases (NMD). Naturally occurring AAV serotypes, like AAV9, typically require enormous doses to treat muscle diseases, like DMD. Improving muscle-specific delivery lowers safety risks by de-targeting the liver and reduces treatment cost due to lower dose requirements.

Indications with gain-of-function mutations, such as Myotonic Dystrophy type 1, require repeat dosing to be effective. However, viral vectors can trigger immune responses preventing repeated administration. BioDrone™, nanovesicles derived from human cells, enables repeated delivery of genetic cargo without triggering significant immune responses.