Optimized genomic editing of a common Duchenne muscular dystrophy mutation in patient-derived muscle cells and a new humanized mouse model

作者：Mateusz Z. Durbacz, Yu Zhang, Hui Li, Takahiko Nishiyama, Ernesto Ortíz, John McAnally, Damir Alzhanov, Ning Liu, Eric N. Olson · 发表于：Molecular Therapy — Nucleic Acids · 年份：2025 · DOI：10.1016/j.omtn.2025.102569 · 被引用次数：5 · 研究领域：CRISPR and Genetic Engineering、Muscle Physiology and Disorders、Pluripotent Stem Cells Research

Cas9)-LRVQR to restore dystrophin expression in patient-derived induced pluripotent stem cells (iPSCs) and a newly generated humanized DMD mouse model. We compared two injection routes for adeno-associated virus (AAV) serotype 9 to deliver gene-editing components to neonatal mice: intraperitoneal (IP) and facial vein (FV) injection. We observed efficient restoration of dystrophin protein expression across multiple skeletal muscle groups and the heart. The AAV9-mediated CRISPR single-cut approach ameliorated key DMD hallmarks, including histopathological phenotypes, impaired grip strength, and elevated serum creatine kinase levels. Our optimized strategies for dystrophin restoration in humanized DMD mice with exon 52 deletion represent a promising treatment for DMD.