AAV-LMNA-miRLMNA

AAV-LMNA-miRLMNA is an experimental gene therapy developed by researchers at UMass Chan Medical School for the treatment of LMNA-associated congenital muscular dystrophy (L-CMD). The therapy employs a silence and replace strategy delivered via a single adeno-associated virus (AAV) vector. It contains an artificial microRNA (amiRNA) designed to silence the expression of endogenous, potentially dominant-negative LMNA alleles, alongside a miRNA-resistant LMNA transgene that utilizes alternative codon usage to avoid silencing. This transgene is engineered to undergo natural alternative splicing to produce both Lamin A and Lamin C proteins. The vector is typically driven by the muscle-specific MHCK7 promoter and packaged in muscle-tropic capsids like Myo4A to target skeletal and cardiac muscle tissues. Preclinical studies in mouse models have shown improvements in survival, body weight, and grip strength.