Superior In vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid.

ABSTRACT: Adeno-associated viral (AAV) vectors are currently being tested in multiple clinical trials for liver-directed gene transfer to treat the bleeding disorders hemophilia A and B and metabolic disorders. The optimal viral capsid for transduction of human hepatocytes has been under active investigation, but results across various models are inconsistent. We tested in vivo transduction in "humanized" mice. Methods to quantitate percent AAV transduced human and murine hepatocytes in chimeric livers were optimized using flow cytometry and confocal microscopy with image analysis. Distinct transduction efficiencies were noted following peripheral vein administration of a self-complementary vector expressing a gfp reporter gene. An engineered AAV3 capsid with two amino acid changes, S663V+T492V (AAV

SUBMITTER: Vercauteren K 

PROVIDER: S-EPMC4923326 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature