In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy
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Checksum (MD5)
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Author(s)
Nelson, C. E.
Hakim, C. H.
Ousterout, D. G.
Thakore, P. I.
Moreb, E. A.
Rivera, R. M. C.
Madhavan, S.
Pan, X.
Ran, F. A.
Yan, W. X.
Date Issued
January 2016
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Nelson, C. E. et al. “In Vivo Genome Editing Improves Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy.” Science 351, 6271 (December 2015): 403–407 © 2016 American Association for the Advancement of Science
Version
Author's final manuscript
Abstract
Duchenne muscular dystrophy (DMD) is a devastating disease affecting about 1 out of 5000 male births and caused by mutations in the dystrophin gene. Genome editing has the potential to restore expression of a modified dystrophin gene from the native locus to modulate disease progression. In this study, adeno-associated virus was used to deliver the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to the mdx mousemodel of DMD to remove the mutated exon 23 from the dystrophin gene. This includes local and systemic delivery to adult mice and systemic delivery to neonatal mice. Exon 23 deletion by CRISPR-Cas9 resulted in expression of the modified dystrophin gene, partial recovery of functional dystrophin protein in skeletal myofibers and cardiac muscle, improvement of muscle biochemistry, and significant enhancement of muscle force.This work establishes CRISPR-Cas9-based genome editing as a potential therapy to treat DMD.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1126/science.aad5143
