Advances in CRISPR/Cas9 Genome Editing for the Treatment of Muscular Dystrophies

• Published in: Human gene therapy Vol. 34; no. 9-10; p. 388
• Main Authors: Fatehi, Sina, Marks, Ryan M, Rok, Matthew J, Perillat, Lucie, Ivakine, Evgueni A, Cohn, Ronald D
• Format: Journal Article
• Language: English
• Published: United States 01-05-2023
• Subjects: Animals; CRISPR-Cas Systems; Dystrophin - genetics; Gene Editing - methods; Genetic Therapy - methods; Muscular Dystrophy, Duchenne - genetics; genome editing; muscular dystrophy; adeno-associated viruses; CRISPR/Cas9; Duchenne muscular dystrophy
• ISSN: 1557-7422
• DOI: 10.1089/hum.2023.059

Muscular dystrophies (MDs) comprise a diverse group of inherited disorders characterized by progressive muscle loss and weakness. Given the genetic etiology underlying MDs, researchers have explored the potential of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing as a therapeutic intervention, resulting in significant advances. Here, we review recent progress on the use of CRISPR/Cas9 genome editing as a potential therapy for MDs. Significant strides have been made in this realm, made possible through innovative techniques such as precision genetic editing by modified forms of CRISPR/Cas9. These approaches have shown varying degrees of success in animal models of MD, including Duchenne MD, congenital muscular dystrophy type 1A, and myotonic dystrophy type 1. Even so, there are several challenges facing the development of CRISPR/Cas9-based MD therapies, including the targeting of satellite cells, improved editing efficiency in skeletal and cardiac muscle tissue, delivery vehicle enhancements, and the host immunogenic response. Although more work is needed to advance CRISPR/Cas9 genome editing past the preclinical stages, its therapeutic potential for MD is extremely promising and justifies concentrated efforts to move into clinical trials.