DMD is an X-linked recessive disorder due to mutations in the dystrophin gene, most of them being large deletions leading to out of frame transcripts. About 80% of the out-of-frame mutations could theoretically be rescued after restoring the translational frame by using exon skipping strategies. The GRMD dog, a large model of DMD, presents a punctual mutation in the acceptor splice site of the dystrophin gene's intron 6, leading to the out of frame elimination of exon 7. We had already improved the dramatic efficacy of the AAV2/1 U7smOPT ESE6 & ESE8 to induce the skipping of exons 6, 7 and 8 allowing production of an in-frame mRNA, to transduce myofibers and to restore at their level expression of a quasi-dystrophin. Functionality of quasi-dystrophin had been demonstrated at the histological scale by restoring the dystrophin associated protein complex, and stopping spontaneous muscle damages. To assess muscle function improvement, we have injected intramuscularly GRMD dogs at the age of 3 weeks in the whole hind limbs anterior compartment with a total dose of 3,5.1012 vg. After two months, normal levels of quasi-dystrophin were recovered throughout the treated muscles. NMR imaging of both hindlimbs was performed at 3T before and after intravenous bolus of Gadolinium-DTPA. Maximal relative enhancement, a parameter we have found to be significantly lower in healthy than in GRMD dogs, was shown to be lower in treated limbs. Functional recovery was assessed by measuring the tetanic force of treated vs untreated muscles after maximal stimulation of the common peroneal nerve. Since tetanic force values were identical for both legs in healthy and control GRMD dogs, they were improved by a factor of 1,6 and 1,4 in treated compared to contralateral untreated legs. Our results point up muscle function recovery after multi exon skipping gene therapy in a large size animal model that recapitulates the main phenotypic features of DMD. These data give all its sense to our strategy and are milestones in perspectives of generalization of the administration.