AAV6-pol2-RNAi

AAV6-pol2-RNAi is an experimental gene therapy construct developed by researchers at the University of Washington for the treatment of Myotonic Dystrophy Type 1 (DM1). It utilizes an adeno-associated virus serotype 6 (AAV6) vector to deliver RNA interference (RNAi) sequences targeting the toxic expanded-repeat DMPK mRNA. By employing a RNA polymerase II (pol 2) promoter instead of the more common U6 polymerase III promoter, the therapy aims to achieve tissue-restricted expression (specifically in skeletal muscle) to minimize off-target effects and potential cardiac toxicity. Preclinical studies in the HSALR mouse model have demonstrated that this approach can effectively reverse aberrant splicing patterns, such as those in Atp2a1 mRNA, and may be combined with MBNL1 protein supplementation for an additive therapeutic effect.