AAV-MT-LiMP-hGAAco

AAV-MT-LiMP-hGAAco is an experimental **gene therapy** based on an adeno-associated virus (AAV) vector engineered for **improved muscle targeting** and **liver detargeting**. It delivers a codon-optimized human acid alpha-glucosidase (hGAAco) gene under the control of a liver-muscle tandem promoter (LiMP), enabling high expression in skeletal and cardiac muscle, with reduced liver expression. The therapy is designed for **Pompe disease (glycogen storage disease type II)**, a lysosomal storage disorder resulting from deficient or absent acid alpha-glucosidase. The LiMP promoter combination allows for a balance between strong muscle expression (the primary site of pathology in Pompe disease) and low but controlled liver expression, which helps both **enable immune tolerance to the transgene** and prevent an anti-GAA immune response. Preclinical studies in Gaa knockout mice have demonstrated that AAV-MT-LiMP-hGAAco leads to robust transgene expression, reduced glycogen accumulation, prevention of cardiomyopathy, and restoration of muscle function[1][2].