M. Koenig, Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals, Cell, vol.50, pp.509-517, 1987.

E. Bonilla, Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface, Cell, vol.54, pp.447-452, 1988.

L. M. Judge, M. Haraguchiln, and J. S. Chamberlain, Dissecting the signaling and mechanical functions of the dystrophin-glycoprotein complex, J. Cell Sci, vol.119, pp.1537-1546, 2006.

M. Eagle, Managing Duchenne muscular dystrophy--the additive effect of spinal surgery and home nocturnal ventilation in improving survival, Neuromuscul. Disord, vol.17, pp.470-475, 2007.

Y. Ishikawa, Duchenne muscular dystrophy: survival by cardiorespiratory interventions, Neuromuscul. Disord, vol.21, pp.47-51, 2011.

X. Xiao, J. Li, and R. J. Samulski, Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector, J. Virol, vol.70, pp.8098-8108, 1996.

Z. Wang, Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart, Nat. Biotechnol, vol.23, pp.321-328, 2005.

M. J. Blankinship, P. Gregorevic, and J. S. Chamberlain, Gene therapy strategies for Duchenne muscular dystrophy utilizing recombinant adeno-associated virus vectors, Mol. Ther, vol.13, pp.241-249, 2006.

C. A. Pacak, Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivo, Circ. Res, vol.99, pp.3-9, 2006.

C. Zincarelli, S. Soltys, G. Rengo, and J. E. Rabinowitz, Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection, Mol. Ther, vol.16, pp.1073-1080, 2008.

A. Toromanoff, Safety and efficacy of regional intravenous (r.i.) versus intramuscular (i.m.) delivery of rAAV1 and rAAV8 to nonhuman primate skeletal muscle, Mol. Ther, vol.16, pp.1291-1299, 2008.

V. M. Rivera, Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer, Blood, vol.105, pp.1424-1430, 2005.

H. Jiang, Evidence of multiyear factor IX expression by AAV-mediated gene transfer to skeletal muscle in an individual with severe hemophilia B, Mol. Ther, vol.14, pp.452-455, 2006.

S. Q. Harper, Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy, Nat. Med, vol.8, pp.253-261, 2002.

T. Athanasopoulos, I. R. Graham, H. Foster, and G. Dickson, Recombinant adeno-associated viral (rAAV) vectors as therapeutic tools for Duchenne muscular dystrophy (DMD), Gene Ther, vol.11, pp.109-121, 2004.

F. Muntoni, S. Torelli, and A. Ferlini, Dystrophin and mutations: one gene, several proteins, multiple phenotypes, Lancet Neurol, vol.2, pp.731-740, 2003.

B. Wang, J. Li, and X. Xiao, Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model, Proc. Natl Acad. Sci. USA, vol.97, pp.13714-13719, 2000.

M. Yoshimura, AAV vector-mediated microdystrophin expression in a relatively small percentage of mdx myofibers improved the mdx phenotype, Mol. Ther, vol.10, pp.821-828, 2004.

P. Gregorevic, rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice, Nat. Med, vol.12, pp.787-789, 2006.

H. Foster, Codon and mRNA sequence optimization of microdystrophin transgenes improves expression and physiological outcome in dystrophic mdx mice following AAV2/8 gene transfer, Mol. Ther, vol.16, pp.1825-1832, 2008.

X. Li, E. M. Eastman, R. J. Schwartz, and R. Draghia-akli, Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences, Nat. Biotechnol, vol.17, pp.241-245, 1999.

T. Koo, Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of alpha1-syntrophin and alphadystrobrevin in skeletal muscles of mdx mice, Hum. Gene Ther, vol.22, pp.1379-1388, 2011.

T. Athanasopoulos, H. Foster, K. Foster, and G. Dickson, Codon optimization of the microdystrophin gene for Duchene muscular dystrophy gene therapy, Methods Mol. Biol, vol.709, pp.21-37, 2011.

T. Koo, Long-term functional adeno-associated virus-microdystrophin expression in the dystrophic CXMDj dog, J. Gene Med, vol.13, pp.497-506, 2011.

J. N. Kornegay, Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies, Mamm. Genome, vol.23, pp.85-108, 2012.

J. W. Mcgreevy, C. H. Hakim, M. A. Mcintosh, and D. Duan, Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy, Dis. Model. Mech, vol.8, pp.195-213, 2015.

Z. Wang, Sustained AAV-mediated dystrophin expression in a canine model of Duchenne muscular dystrophy with a brief course of immunosuppression, Mol. Ther, vol.15, pp.1160-1166, 2007.

Z. Wang, Successful regional delivery and long-term expression of a dystrophin gene in canine muscular dystrophy: a preclinical model for human therapies, Mol. Ther, vol.20, pp.1501-1507, 2012.

J. H. Shin, A simplified immune suppression scheme leads to persistent micro-dystrophin expression in Duchenne muscular dystrophy dogs. Hum, Gene Ther, vol.23, pp.202-209, 2012.

J. H. Shin, Microdystrophin ameliorates muscular dystrophy in the canine model of duchenne muscular dystrophy, Mol. Ther, vol.21, pp.750-757, 2013.

D. Wang, L. Zhong, M. A. Nahid, and G. Gao, The potential of adeno-associated viral vectors for gene delivery to muscle tissue, Expert Opin. Drug Deliv, vol.11, pp.345-364, 2014.

H. Hayashita-kinoh, Intra-amniotic rAAV-mediated microdystrophin gene transfer improves canine X-linked muscular dystrophy and may induce immune tolerance, Mol. Ther, vol.23, pp.627-637, 2015.

L. Guiner and C. , Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients, Mol. Ther, vol.22, pp.1923-1935, 2014.
URL : https://hal.archives-ouvertes.fr/inserm-02447482

Z. Fan, Safety and feasibility of high-pressure transvenous limb perfusion with 0.9% saline in human muscular dystrophy, Mol. Ther, vol.20, pp.456-461, 2012.

Z. Fan, High-pressure transvenous perfusion of the upper extremity in human muscular dystrophy: a safety study with 0.9% saline. Hum, Gene Ther, vol.26, pp.614-621, 2015.

F. Nguyen, Y. Cherel, L. Guigand, I. Goubault-leroux, and M. Wyers, Muscle lesions associated with dystrophin deficiency in neonatal golden retriever puppies, J. Comp. Pathol, vol.126, pp.100-108, 2002.

V. Dubowitz, C. A. Sewry, A. Oldfors, and L. Russell, Muscle Biopsy: A Practical Approach 4th edn, pp.250-275, 2013.

J. L. Thibaud, Comprehensive longitudinal characterization of canine muscular dystrophy by serial NMR imaging of GRMD dogs, Neuromuscul. Disord, vol.22, pp.85-99, 2012.

C. Wary, Splitting of Pi and other (3)(1)P NMR anomalies of skeletal muscle metabolites in canine muscular dystrophy, NMR Biomed, vol.25, pp.1160-1169, 2012.

K. Rouger, Systemic delivery of allogenic muscle stem cells induces longterm muscle repair and clinical efficacy in duchenne muscular dystrophy dogs, Am. J. Pathol, vol.179, pp.2501-2518, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00712818

N. M. Vieira, Jagged 1 rescues the Duchenne muscular dystrophy phenotype, Cell, vol.163, pp.1204-1213, 2015.

I. Barthelemy, Gait analysis using accelerometry in dystrophin-deficient dogs, Neuromuscul. Disord, vol.19, pp.788-796, 2009.
URL : https://hal.archives-ouvertes.fr/hal-01193362

I. Barthelemy, Longitudinal ambulatory measurements of gait abnormality in dystrophin-deficient dogs, BMC Musculoskelet. Disord, vol.12, p.75, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00596534

Y. M. Kobayashi, Sarcolemma-localized nNOS is required to maintain activity after mild exercise, Nature, vol.456, pp.511-515, 2008.

A. Vulin, Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping, Mol. Ther, vol.20, pp.2120-2133, 2012.

T. Larcher, Characterization of dystrophin deficient rats: a new model for Duchene muscular dystrophy, PLoS ONE, vol.9, p.110371, 2014.

J. N. Kornegay, Widespread muscle expression of an AAV9 human minidystrophin vector after intravenous injection in neonatal dystrophin-deficient dogs, Mol. Ther, vol.18, pp.1501-1508, 2010.

M. J. Day, Immune system development in the dog and cat, J. Comp. Pathol, vol.137, pp.10-15, 2007.

Y. Yue, Safe and bodywide muscle transduction in young adult Duchenne muscular dystrophy dogs with adeno-associated virus, Hum. Mol. Genet, vol.24, pp.5880-5890, 2015.

P. J. Felsburg, Overview of immune system development in the dog: comparison with humans, Hum. Exp. Toxicol, vol.21, pp.487-492, 2002.

V. Haurigot, Safety of AAV factor IX peripheral transvenular gene delivery to muscle in hemophilia B dogs, Mol. Ther, vol.18, pp.1318-1329, 2010.

A. Toromanoff, Lack of immunotoxicity after regional intravenous (RI) delivery of rAAV to nonhuman primate skeletal muscle, Mol. Ther, vol.18, pp.151-160, 2010.

V. R. Arruda, Peripheral transvenular delivery of adeno-associated viral vectors to skeletal muscle as a novel therapy for hemophilia B, Blood, vol.115, pp.4678-4688, 2010.

F. Fougerousse, Phenotypic correction of alpha-sarcoglycan deficiency by intra-arterial injection of a muscle-specific serotype 1 rAAV vector, Mol. Ther, vol.15, pp.53-61, 2007.
URL : https://hal.archives-ouvertes.fr/hal-01610043

V. Arechavala-gomeza, Revertant fibres and dystrophin traces in Duchenne muscular dystrophy: implication for clinical trials, Neuromuscul. Disord, vol.20, pp.295-301, 2010.

C. L. Halbert, M. J. Metzger, S. L. Lam, and A. D. Miller, Capsid-expressing DNA in AAV vectors and its elimination by use of an oversize capsid gene for vector production, Gene Ther, vol.18, pp.411-417, 2011.

Z. Wang, Elimination of contaminating cap genes in AAV vector virions reduces immune responses and improves transgene expression in a canine gene therapy model, Gene Ther, vol.21, pp.363-370, 2014.

A. C. Nathwani, Long-term safety and efficacy of factor IX gene therapy in hemophilia B, N. Engl. J. Med, vol.371, 1994.

L. G. Chicoine, Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery, Mol. Ther, vol.22, pp.338-347, 2014.

R. J. Bartlett, In vivo targeted repair of a point mutation in the canine dystrophin gene by a chimeric RNA/DNA oligonucleotide, Nat. Biotechnol, vol.18, pp.615-622, 2000.

B. Fraysse, Gait characterization in golden retriever muscular dystrophy dogs using linear discriminant analysis, BMC Musculoskelet. Disord, vol.18, p.153, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01524325

W. P. Thomas, Recommendations for standards in transthoracic twodimensional echocardiography in the dog and cat. Echocardiography Committee of the Specialty of Cardiology, J. Vet. Intern. Med, vol.7, pp.247-252, 1993.

L. Goubin, C. Guigand-;-c.-couzinié, C. Domenger, M. Gazaille, N. Guilbaud et al., ) for their technical assistance. We thank the MDA Monoclonal Antibody Resource for providing the MANEX 1011C antibody. Finally, we also thank S. Roques for its valuable contribution during the implementation of this study, This project was supported by AFM-Téléthon (Association Franc¸aise contre les Myopathies), the MDUK (Muscular Dystrophy UK), the French Agence Nationale pour la Recherche