In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy.

TitleIn vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy.
Publication TypeJournal Article
Year of Publication2016
AuthorsNelson, CE, Hakim, CH, Ousterout, DG, Thakore, PI, Moreb, EA, Castellano Rivera, RM, Madhavan, S, Pan, X, Ran, FA, Yan, WX, Asokan, A, Zhang, F, Duan, D, and Gersbach, CA
JournalScience
Volume351
Issue6271
Start Page403
Pagination403 - 407
Date Published01/2016
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 mouse model 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.

DOI10.1126/science.aad5143
Short TitleScience