midi-dystrophin ΔSR5-15

Midi-dystrophin ΔSR5-15 is a gene therapy candidate designed for the treatment of Duchenne muscular dystrophy (DMD). Unlike micro-dystrophins, which are small enough to fit into a single adeno-associated virus (AAV) vector but lack many functional domains, midi-dystrophins are larger, more functional versions of the dystrophin protein. Because the coding sequence for midi-dystrophin exceeds the 4.7 kb packaging capacity of a single AAV, this approach utilizes a dual-AAV or triple-AAV system. The protein is reconstituted in vivo using split-intein-mediated protein trans-splicing. Specifically, the ΔSR5-15 variant lacks spectrin repeats 5 through 15, making it significantly larger and potentially more effective than the micro-dystrophins currently in clinical trials. Research has demonstrated that delivery using potent myotropic vectors like AAVMYO can achieve body-wide expression in striated muscles at low doses, leading to significant physiological improvements in dystrophic models.

Other names

midi-dystrophinlarge dystrophin