@article{78bc1ad2c08c499f8fb247040ccadc40,
title = "CRISPR-Cas9 corrects Duchenne muscular dystrophy exon 44 deletion mutations in mice and human cells",
abstract = "Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), which is characterized by lethal degeneration of cardiac and skeletal muscles. Mutations that delete exon 44 of the dystrophin gene represent one of the most common causes of DMD and can be corrected in ~12% of patients by editing surrounding exons, which restores the dystrophin open reading frame. Here, we present a simple and efficient strategy for correction of exon 44 deletion mutations by CRISPR-Cas9 gene editing in cardiomyocytes obtained from patient-derived induced pluripotent stem cells and in a new mouse model harboring the same deletion mutation. Using AAV9 encoding Cas9 and single guide RNAs, we also demonstrate the importance of the dosages of these gene editing components for optimal gene correction in vivo. Our findings represent a significant step toward possible clinical application of gene editing for correction of DMD.",
author = "Min, {Yi Li} and Hui Li and Cristina Rodriguez-Caycedo and Mireault, {Alex A.} and Jian Huang and Shelton, {John M.} and McAnally, {John R.} and Leonela Amoasii and Mammen, {Pradeep P.A.} and Rhonda Bassel-Duby and Olson, {Eric N.}",
note = "Funding Information: We thank J. Cabrera for graphics, C. Nolen for technical assistance, D. Tennison for genotyping, V. S. Malladi for bioinformatic analysis, Neuro-Models Facility and L. Ingle for grip strength experiments, Flow Cytometry Core and A. Mobley for FACS, C. Wang and the Boston Children{\textquoteright}s Hospital Viral Core for AAV production, D. Caballero for qPCR analysis, E. Sanchez-Ortiz for assistance in the Western blot, and C. Long, Y. Zhang, V. Kyrychenko, and N. Jones for the constructive advice. We are grateful to S. Hauschka (University of Washington) for the CK8e regulatory cassette and to D. Grimm (Heidelberg University Hospital, Germany) for the TRISPR plasmid. This work was supported by the NIH (grants HL130253 and AR-067294), the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center (grant U54 HD 087351), the Parent Project Muscular Dystrophy Award, CureDuchenne, Exonics Therapeutics, and the Robert A. Welch Foundation (grant 1-0025 to E.N.O.). Publisher Copyright: Copyright {\textcopyright} 2019 The Authors, some rights reserved.",
year = "2019",
doi = "10.1126/sciadv.aav4324",
language = "English (US)",
volume = "5",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "3",
}