Universal Prime Editing Therapeutic Strategy for RyR1-Related Myopathies: A Protective Mutation Rescues Leaky RyR1 Channel.

ABSTRACT: RyR1-related myopathies (RyR1-RMs) include a wide range of genetic disorders that result from mutations in the RYR1 gene. Pathogenic variants lead to defective intracellular calcium homeostasis and muscle dysfunction. Fixing intracellular calcium leaks by stabilizing the RyR1 calcium channel has been identified as a promising therapeutic target. Gene therapy via prime editing also holds great promise as it can cure diseases by correcting genetic mutations. However, as more than 700 variants have been identified in the RYR1 gene, a universal treatment would be a more suitable solution for patients. Our investigation into the RyR1-S2843A mutation has yielded promising results. Using a calcium leak assay, we determined that the S2843A mutation was protective when combined with p

SUBMITTER: Godbout K 

PROVIDER: S-EPMC11988564 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature