micro-dystrophin (AAV-mediated)

Micro-dystrophin (AAV-mediated) refers to a class of gene therapies designed to treat Duchenne muscular dystrophy (DMD). DMD is caused by mutations in the DMD gene, which encodes the dystrophin protein essential for muscle membrane stability. Because the full-length dystrophin cDNA (~14 kb) exceeds the packaging capacity of adeno-associated virus (AAV) vectors (~4.7 kb), these therapies utilize a truncated 'micro-dystrophin' transgene containing essential functional domains. The therapy typically involves a single intravenous or intrathecal infusion of a recombinant AAV (e.g., AAVrh74, AAV9) carrying the micro-dystrophin transgene under the control of a muscle-specific promoter. The goal is to restore a functional, albeit shortened, version of dystrophin at the sarcolemma to improve muscle function and slow disease progression. Sarepta Therapeutics' Elevidys (delandistrogene moxeparvovec) is the first approved product in this class, while other candidates are being developed by companies such as Solid Biosciences, REGENXBIO, Genethon, and Insmed.