AAV-midi-dystrophin

AAV-midi-dystrophin (KNA-123) is an investigational dual-vector adeno-associated virus (AAV) gene therapy being developed by Kinea Bio, in collaboration with the University of Washington, for the treatment of Duchenne muscular dystrophy (DMD). Due to the large size of the dystrophin gene (11.2 kb coding sequence), which exceeds the packaging capacity of a single AAV vector (~4.7 kb), conventional gene therapies are limited to delivering a highly truncated 'micro-dystrophin'. To overcome this limitation, KNA-123 utilizes Kinea's proprietary Split Intein-Mediated Protein Ligation for Gene Therapy (SIMPLI-GT) platform. This approach employs two separate AAV vectors, each encoding a portion of a larger, more functional 'midi-dystrophin' protein fused to split inteins. Once inside the target muscle cells, the split inteins undergo protein trans-splicing to seamlessly assemble the full-length midi-dystrophin protein. Preclinical studies have demonstrated that midi-dystrophin contains more functional domains than micro-dystrophin, offering superior therapeutic efficacy and muscle protection at significantly lower viral doses.