Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy
Year: 2015
Type: article
Abstract: CRISPR/Cas9-mediated genome editing holds clinical potential for treating genetic diseases, such as Duchenne muscular dystrophy (DMD), which is caused by mutations in the dystrophin gene. To correct DMD by skipping mutant dystrophin exons in postnatal muscle tissue in vivo, we used adeno-associated virus-9 (AAV9) to deliver gene-editing components to postnatal mdx mice, a model of DMD. Different modes of AAV9 delivery were systematically tested, including intraperitoneal at postnatal day 1 (P1), intramuscular at P12, and retro-orbital at P18. Each of these methods restored dystrophin protein expression in cardiac and skeletal muscle to varying degrees, and expression increased from 3 to 12 weeks after injection. Postnatal gene editing also enhanced skeletal muscle function, as measured by grip strength tests 4 weeks after injection. This method provides a potential means of correcting mutations responsible for DMD and other monogenic disorders after birth.
Source: Science
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: Deciphering a Regulatory Circuit for Myocardial Metabolism and Energy Homeostasis, Heart Repair through Reprogramming of Cardiac Cell Fate, MicroRNA Control of Cardiac Gene Expression, Function and Disease, Microenvironmental control of progenitors in organ dysfunction and repair, G662211534, Metabolic Control by Myogenic MicroRNAs, Mediator and Myokines, CORE GRANT FOR VISION RESEARCH, Myoediting of Duchenne muscular dystrophy
OpenAlex ID: W2196662084