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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Nelson, CE; Hakim, CH; Ousterout, DG; Thakore, PI; Moreb, EA; Castellanos Rivera, RM; Madhavan, S; Pan, X; Ran, FA; Yan, WX; Asokan, A; Zhang, F; Duan, D; Gersbach, CA

Published Date

  • January 22, 2016

Published In

Volume / Issue

  • 351 / 6271

Start / End Page

  • 403 - 407

PubMed ID

  • 26721684

Pubmed Central ID

  • PMC4883596

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aad5143


  • eng

Conference Location

  • United States