Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy

Niclas E. Bengtsson, John K. Hall, Guy L. Odom, Michael P. Phelps, Colin R. Andrus, R. David Hawkins, Stephen D. Hauschka, Joel R. Chamberlain and Jeffrey S. Chamberlain ()
Additional contact information
Niclas E. Bengtsson: University of Washington
John K. Hall: University of Washington
Guy L. Odom: University of Washington
Michael P. Phelps: University of Washington
Colin R. Andrus: University of Washington
R. David Hawkins: University of Washington
Stephen D. Hauschka: Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington
Joel R. Chamberlain: Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington
Jeffrey S. Chamberlain: University of Washington

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx4cv mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation. Muscle-restricted Cas9 expression enables direct editing of the mutation, multi-exon deletion or complete gene correction via homologous recombination in myogenic cells. Treated muscles express dystrophin in up to 70% of the myogenic area and increased force generation following intramuscular delivery. Furthermore, systemic administration of the vectors results in widespread expression of dystrophin in both skeletal and cardiac muscles. Our results demonstrate that AAV-mediated muscle-specific gene editing has significant potential for therapy of neuromuscular disorders.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/ncomms14454 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14454

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14454

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().