Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy
Open accessAbstract
Gene editing and muscular dystrophy: Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness and a shortened life span. The disease is caused by mutations that reduce or prevent expression of dystrophin, an essential structural protein in skeletal and heart muscle. The gene editing technology CRISPR-Cas9 can correct disease-causing mutations and has yielded promising results in mouse models of DMD. In a small, short-term study, Amoasii et al. tested this strategy in a dog model of DMD that exhibits many features of the human disease. Intramuscular or systemic delivery of the gene editing components resulted in a substantial increase in dystrophin protein levels in skeletal and heart muscle. Restoration of dystrophin expression was accompanied by improved muscle histology. Science , this issue p. 86
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In dogs with the ΔEx50 mutation, virus-mediated systemic CRISPR-Cas9 delivery restored dystrophin levels to 3-90% of normal and improved muscle tissue appearance.
“After virus-mediated systemic delivery in skeletal muscle, dystrophin levels were restored to 3-90% of normal, and the muscle tissue appearance in treated dogs was improved.”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [50]
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- Authors
- Amoasii, L., Hildyard, J. C. W., Li, H., Sanchez-Ortiz, E., Mireault, A., Caballero, D., Harron, R., Stathopoulou, T.-R., Massey, C., Shelton, J. M., Bassel-Duby, R., Piercy, R. J., & Olson, E. N.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Royal Veterinary College (GB)
- Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
- Corresponding author
- Olson, Eric N.
- ORCID
- Venue
- Science
- Published
- 2018-10-05
- Volume
- 362
- Issue
- 6410
- Pages
- 86-91
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6205228
- OpenAlex
- W2889510460
- Cited by
- 546
- References
- 35
- Citations by year
- 2026: 20 · 2025: 46 · 2024: 38 · 2023: 60 · 2022: 90 · 2021: 88 · 2020: 88 · 2019: 101 · 2018: 14
- FWCI
- 25.96
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (HL130253, HL077439, DK099653, AR067294 and U54HD087351)
- Welch Foundation (1-0025)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- Duchenne muscular dystrophy, dystrophin, CRISPR/Cas9 genome editing, canine model, intramuscular administration, systemic drug delivery, skeletal muscle, myocardium, muscle histology
- MeSH terms
- Gene Editing, Adenoviridae, Animals, Disease Models, Animal, Dogs, Female, Male, Dystrophin, Gene Transfer Techniques, Muscular Dystrophy, Duchenne, CRISPR-Cas Systems
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