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Duchenne Muscular Dystrophy (DMD) is a severe, progressive, genetic neuromuscular disease caused by mutations in the DMD gene encoding dystrophin and affects ~1 in 5,000 males. There is no cure for DMD, but gene therapy using Adeno self-complementary Associated Virus (scAAV) has been investigated. While the DMD gene is too large for scAAV gene-replacement, exon skipping strategies have gained popularity as promising therapeutic alternatives. The aim of exon skipping is to restore dystrophin expression by removing out-of-frame exons, leading to the production of a truncated but partially functional protein. Past studies have demonstrated that exon skipping can be efficiently induced by delivering scAAV encoding antisense sequences embedded in U7snRNA (scAAV.U7snRNA). A clinical trial is underway using scAAV.U7snRNA to treat DMD patients harboring exon 2 duplications. Here we have focused on skipping exons 6-8, which could benefit 3-4% of DMD patients. We screened the ability of several scAAV.U7snRNA constructs to skip exons 6-8 in myotubes derived from control human fibroblasts. We identified several scAAV.U7snRNA able to skip exons 6-8. In parallel, to model the subset of patients with mutations treatable by skipping exons 6-8, we created a mouse model with the murine DMD gene knocked out and a human DMD gene harboring a nonsense mutation in exon 7 (hDMDm7 mouse) using CRISPR/Cas9. Western blot did not detect any dystrophin expression in the hDMDm7 mouse. Additionally, the hDMDm7 mouse demonstrated high levels of centronucleation and diminished resistance to fatigue following consecutive eccentric contractions, both of which are hallmarks of DMD pathology. scAAV.U7snRNA constructs that most efficiently induced exon skipping in vitro were injected into tibialis anterior muscles of 6-week-old hDMDm7 mice and mice were dissected at 12 weeks of age. Exon skipping analysis by RT-PCR found the presence of a corrected, in-frame transcript post-injection. This result indicates that scAAV.U7snRNA can induce simultaneous skipping of three exons in vivo and may have therapeutic implications for ~3-4% of DMD patients.