Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase.

ABSTRACT: Glycogen storage disease type II or Pompe disease is a severe neuromuscular disorder caused by mutations in the lysosomal enzyme, acid α-glucosidase (GAA), which result in pathological accumulation of glycogen throughout the body. Enzyme replacement therapy is available for Pompe disease; however, it has limited efficacy, has high immunogenicity, and fails to correct pathological glycogen accumulation in nervous tissue and skeletal muscle. Using bioinformatics analysis and protein engineering, we developed transgenes encoding GAA that could be expressed and secreted by hepatocytes. Then, we used adeno-associated virus (AAV) vectors optimized for hepatic expression to deliver the GAA transgenes to Gaa knockout (Gaa^-/-) mice, a model of Pompe disease. Therapeutic gene trans

SUBMITTER: Puzzo F 

PROVIDER: S-EPMC5826611 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature