AAV.DB3.miMSH3

AAV.DB3.miMSH3 (also known as AAV-DB-3.miMSH3) is an investigational gene therapy developed by Latus Bio for the treatment of Huntington's disease (HD). The therapy utilizes a proprietary, engineered adeno-associated virus (AAV) capsid, AAV-DB-3, which is designed to specifically and efficiently target medium spiny neurons (MSNs) in the striatum, the primary site of neurodegeneration in HD. The therapeutic payload is an artificial microRNA (miMSH3) that targets the mRNA of MutS Homolog 3 (MSH3). MSH3 is a protein involved in DNA mismatch repair that has been identified as a critical driver of the somatic expansion of CAG repeats in the huntingtin (HTT) gene. By knocking down MSH3 expression, AAV.DB3.miMSH3 aims to reduce somatic instability and slow disease progression. Preclinical studies in non-human primates and mouse models have demonstrated significant MSH3 mRNA reduction and a decrease in somatic expansion, supporting its potential as a disease-modifying treatment for HD.