Affiliations: [a] Molecular Biology Interdepartmental Program, University of California, Los Angeles, CA, USA
| [b] Center for Duchenne Muscular Dystrophy at UCLA, University of California, Los Angeles, CA, USA
| [c] Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, LosAngeles, CA, USA
| [d] Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| [e] Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| [f] Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Correspondence:
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Correspondence to: Melissa J. Spencer, 635 Charles E. Young Dr. South, 703422, Los Angeles, CA 90095, USA. Tel.: +1 310 267 4582; Fax: +1 310 206 1998; E-mail: mspencer@mednet.ucla.edu.
Abstract: Duchenne muscular dystrophy is caused by mutations in DMD which disrupt the reading frame. Therapeutic strategies that restore DMD’s reading frame, such as exon skipping and CRISPR/Cas9, need to be tested in the context of the human DMD sequence in vivo. We have developed a novel dystrophic mouse model by using CRISPR/Cas9 to delete exon 45 in the human DMD gene in hDMD mice, which places DMD out-of-frame. We have utilized this model to demonstrate that our clinically-relevant CRISPR/Cas9 platform, which targets deletion of human DMD exons 45–55, can be directly applied in vivo to restore dystrophin.
