Systemic MyoAAV-saRNA delivery activates endogenous utrophin and rescues dystrophic pathology in mdx mice.

ABSTRACT:

Background

Therapeutic activation of endogenous utrophin, a homolog of dystrophin, represents a mutation-agnostic therapeutic strategy with considerable potential for treating Duchenne muscular dystrophy (DMD). However, the large size of current dCas9-based activation systems hinders efficient adeno-associated virus (AAV) delivery, and the long-term feasibility and therapeutic durability of such treatments remain uncertain. To overcome these limitations, we developed a muscle-targeted utrophin activation platform based on small activating RNA (saRNA), termed MyoAAV-saRNA.

Methods

Screening of a panel of saRNAs targeting the Utrn promoter identified Utrophin-257 as the most effective variant, capable of inducing more than a 3.7-fold increase in dystrophin mRNA expressi

SUBMITTER: Xiahou Z 

PROVIDER: S-EPMC12636391 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature