In vivo gene editing in dystrophic mouse muscle and muscle stem cells

Tabebordbar, Mohammadsharif; Zhu, Kexian; Cheng, Jason; Chew, Wei Leong; Widrick, Jeffrey J.; Yan, Winston X.; Maesner, Claire; Wu, Elizabeth Y.; Xiao, Ru; Ran, F. Ann; Cong, Le; Zhang, Feng; Vandenberghe, Luk H.; Church, George M.; Wagers, Amy J.

doi:10.1126/science.aad5177

articleScienceDec 31, 2015Closed access

In vivo gene editing in dystrophic mouse muscle and muscle stem cells

MTMohammadsharif Tabebordbar KZKexian Zhu JCJason Cheng WLWei Leong Chew JJJeffrey J. Widrick

Harvard University · Harvard Stem Cell Institute · +4 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated, but still functional, protein. In this study, we developed and tested a direct gene-editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored the Dmd reading…

Citation impact

1,039

total citations

FWCI: 66.55
Percentile: 100%
References: 55

Citations per year

Authors

15

Topics & keywords

Topics

Keywords

Duchenne muscular dystrophy
CRISPR
Dystrophin
Biology
mdx mouse
Genome editing
Exon
Skeletal muscle

UN Sustainable Development Goals

Good health and well-being

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