AAV8.U7snRNA

AAV8.U7snRNA (also known as AT466) is an investigational adeno-associated virus serotype 8 (AAV8)-vectorized gene therapy designed for the treatment of myotonic dystrophy type 1 (DM1). Developed by Astellas Gene Therapies (formerly Audentes Therapeutics) in collaboration with Nationwide Children's Hospital, the therapy utilizes modified mouse U7 small nuclear RNAs (U7snRNA) to deliver antisense sequences targeting the dystrophia myotonica protein kinase (DMPK) gene. The construct is designed to employ two complementary mechanisms: vectorized exon skipping to induce out-of-frame skipping and subsequent transcript degradation of DMPK, and vectorized RNA knockdown via steric hindrance at the 3' untranslated region (3'UTR) to prevent the sequestration of muscleblind-like 1 (MBNL1) protein by toxic CUG repeat expansions. This dual approach aims to reduce nuclear RNA foci accumulation and restore normal alternative splicing profiles in affected muscle tissues.

Other names

AAV8-U7snRNAAAV-8-U7snRNAAAV 8-U7snRNAAAV8.U7snRNAsAAV-8.U7snRNAsAAV 8.U7snRNAsscAAV8-U7snRNAscAAV-8-U7snRNAscAAV 8-U7snRNA