@article { , title = {Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy}, abstract = {Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90\% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92\% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD.}, doi = {10.1126/science.aau1549}, issn = {0036-8075}, issue = {6410}, journal = {SCIENCE}, pages = {86-91}, publicationstatus = {Published}, publisher = {American Association for the Advancement of Science}, url = {https://rvc-repository.worktribe.com/output/1385693}, volume = {362}, keyword = {Musculoskeletal Biology, ePrints migration}, year = {2018}, author = {Amoasii, L and Hildyard, J C W and Li, H and Sanchez-Ortiz, E and Mireault, A and Caballero, D and Harron, R and Stathopoulou, T-R and Massey, C A and Shelton, J M and Bassel-Duby, R and Piercy, R J and Olson, E N} }