AAV9 Edits Muscle Stem Cells in Normal and Dystrophic Adult Mice

Michael E. Nance, Ruicheng Shi, Chady H. Hakim, Nalinda B. Wasala, Yongping Yue, Xiufang Pan, Tracy Zhang, Carolyn A. Robinson, Sean X. Duan, Gang Yao, N. Nora Yang, Shi jie Chen, Kathryn Rae Wagner, Charles A. Gersbach, Dongsheng Duan

Research output: Contribution to journalArticle

Abstract

Satellite cells are stem cells responsible for muscle repair and maintenance. Here, Nance et al. show that adeno-associated virus serotype-9 (AAV9) efficiently transduced and edited satellite cells. Intravenous delivery of AAV9 CRISPR vectors to mdx mice, a model for Duchenne muscular dystrophy, not only corrected dystrophin gene mutation in mature muscle cells but also in satellite cells. Importantly, the muscle regenerated from the edited satellite cells contained the CRISPR-corrected dystrophin gene and expressed the edited dystrophin protein. Satellite cell editing provides a means to achieve enduring muscle gene therapy that can meet the demands of muscle injury and maintenance throughout a patient's life.

Original languageEnglish (US)
JournalMolecular Therapy
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • AAV
  • Ai14
  • Cas9
  • Cre
  • CRISPR
  • DMD
  • dystrophin
  • gene editing
  • gRNA
  • mdx
  • MuSC
  • muscle
  • muscle graft
  • muscle stem cell
  • Pax7
  • Pax7-ZsGreen
  • regeneration
  • satellite cell
  • stem cell
  • stem cell renewal

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Nance, M. E., Shi, R., Hakim, C. H., Wasala, N. B., Yue, Y., Pan, X., ... Duan, D. (2019). AAV9 Edits Muscle Stem Cells in Normal and Dystrophic Adult Mice. Molecular Therapy. https://doi.org/10.1016/j.ymthe.2019.06.012