AAV-MSH3 splice modulator

AAV-MSH3 splice modulator is an adeno-associated virus (AAV) vector-delivered gene therapy designed to treat repeat expansion disorders, such as Huntington’s Disease (HD) and myotonic dystrophy Type I (DM1). Developed by Ascidian Therapeutics, the therapy utilizes a U7 snRNA-based splice modulator to target MSH3 pre-mRNA. This mechanism induces exon skipping, which triggers nonsense-mediated decay (NMD) and subsequently reduces MSH3 protein levels. MSH3 is a key component of the DNA mismatch repair pathway and a known genetic modifier of somatic repeat expansion. By lowering MSH3 levels, the therapy aims to inhibit the somatic instability of trinucleotide repeats, potentially slowing or halting disease progression. Preclinical studies have demonstrated significant MSH3 reduction in human iPSC-derived neurons and non-human primate brains.

Other names

MSH3 splice modulatorMSH-3 splice modulatorMSH 3 splice modulatorAAV-encoded MSH3 splice modulator