Development of an AAV-delivered microRNA gene therapy for myotonic dystrophy type 1.

ABSTRACT: Myotonic dystrophy type 1 (DM1), characterized by life-threatening muscle weakness, compromised respiration, and, often, cardiac conduction abnormalities, is the most common form of adult muscular dystrophy. DM1 is caused by a CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene, resulting in aggregation of DMPK mRNA into insoluble ribonuclear foci that sequester RNA-binding proteins. Redistribution of essential splicing factors causes mis-splicing of factors responsible for muscle differentiation. Targeting the disease at its root by reducing DMPK RNA promises to reduce RNA foci and pathogenesis. Here, we present an adeno-associated virus (AAV)-RNAi-based strategy for DMPK reduction based on a muscle-targeted platform comprising an AAV

SUBMITTER: Tomassy GS 

PROVIDER: S-EPMC12703144 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature