This novel exon-skipping gene therapy strategy for treating Duchenne muscular dystrophy (DMD) targets exon 12 of the DMD gene, allowing full restoration of the native reading frame and facilitating expression of a full length dystrophin protein in single-exon duplication. In multi-exon deletions, skipping exon 12 can revitalize a functional open reading frame to produce a partially functional dystrophin, potentially with higher expression levels than current antisense oligonucleotide therapies. Building on prior success with an AAV.U7snRNA exon‑2 skipping therapy, the new IP identifies specific exon‑12 and intronic sequences within the DMD locus suitable for therapeutic exon skipping, incorporates these into optimized U7snRNA (SmOpt) cassettes, and enables expression via diverse AAV serotypes including AAV1, AAV2, AAV5, AAV6, AAVrh74, AAV8, AAV9, and myotropic variants.