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

Publication ,  Journal Article
Nelson, CE; Hakim, CH; Ousterout, DG; Thakore, PI; Moreb, EA; Castellanos Rivera, RM; Madhavan, S; Pan, X; Ran, FA; Yan, WX; Asokan, A ...
Published in: Science
January 22, 2016

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.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

January 22, 2016

Volume

351

Issue

6271

Start / End Page

403 / 407

Location

United States

Related Subject Headings

  • Sequence Deletion
  • Muscular Dystrophy, Duchenne
  • Muscle, Skeletal
  • Mice, Inbred mdx
  • Mice
  • Male
  • Genetic Therapy
  • General Science & Technology
  • Exons
  • Dystrophin
 

Citation

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Nelson, C. E., Hakim, C. H., Ousterout, D. G., Thakore, P. I., Moreb, E. A., Castellanos Rivera, R. M., … Gersbach, C. A. (2016). In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science, 351(6271), 403–407. https://doi.org/10.1126/science.aad5143
Nelson, Christopher E., Chady H. Hakim, David G. Ousterout, Pratiksha I. Thakore, Eirik A. Moreb, Ruth M. Castellanos Rivera, Sarina Madhavan, et al. “In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy.Science 351, no. 6271 (January 22, 2016): 403–7. https://doi.org/10.1126/science.aad5143.
Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Castellanos Rivera RM, et al. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. 2016 Jan 22;351(6271):403–7.
Nelson, Christopher E., et al. “In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy.Science, vol. 351, no. 6271, Jan. 2016, pp. 403–07. Pubmed, doi:10.1126/science.aad5143.
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. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. 2016 Jan 22;351(6271):403–407.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

January 22, 2016

Volume

351

Issue

6271

Start / End Page

403 / 407

Location

United States

Related Subject Headings

  • Sequence Deletion
  • Muscular Dystrophy, Duchenne
  • Muscle, Skeletal
  • Mice, Inbred mdx
  • Mice
  • Male
  • Genetic Therapy
  • General Science & Technology
  • Exons
  • Dystrophin