AAV1.U7snRNA

AAV1.U7snRNA is an experimental gene therapy candidate designed for the treatment of myotonic dystrophy type 1 (DM1). It utilizes an adeno-associated virus serotype 1 (AAV1) vector to deliver modified U7 small nuclear RNAs (U7snRNA) engineered with antisense sequences. These sequences are specifically designed to target the 3'UTR region of the DMPK gene, promoting steric hindrance of toxic CUG repeat expansions. By interfering with the expanded CUG mRNA, the therapy aims to reduce the formation of toxic nuclear DMPK foci and restore the localization of Muscleblind-like protein 1 (MBNL1). This restoration allows for the correction of downstream splicing defects in critical genes such as Serca1 and Clcn1. Preclinical studies in the HSAlr mouse model and patient-derived cell lines have demonstrated that intramuscular administration of AAV1.U7snRNA can significantly reduce myotonia and improve muscle physiological properties.