Targeted Therapeutic Strategy for Duchenne Muscular Dystrophy Leveraging RNA Editing

Abstract

Duchenne muscular dystrophy (DMD) is a devastation X-linked recessive genetic disorder involving progressive muscle tissue degeneration and premature death, primarily occurring in males. Current therapies such as corticosteroids and gene replacement are of limited value and suffer from the problems of enormous side effects and restrictions based on viral vectors. RNA base editing is a new-generation therapeutic strategy for genetic diseases like DMD with advantages of being reversible, less likely to lead to off-target risks than DNA editing, and direct disease-causing mRNA mutation correction. This study reviews the literature for RNA base editing as a therapy for DMD. Major RNA editing technologies, adenosine-to-inosine (A-to-I) editing by engineered ADAR enzymes , are introduced for their potential to edit out premature stop codons in the DMD mRNA to restore functional dystrophin protein expression. Key milestones include the miniaturization of editors suitable for adeno-associated virus (AAV) delivery, demonstration of efficacy in humanized DMD mouse models with dystrophin restoration and functional muscle improvement. The findings reveal the therapeutic utility of RNA base editing for DMD and propose new directions for its future clinical application.