A humanized mouse model for adeno-associated viral gene therapy.

ABSTRACT: Clinical translation of AAV-mediated gene therapy requires preclinical development across different experimental models, often confounded by variable transduction efficiency. Here, we describe a human liver chimeric transgene-free Il2rg^-/-/Rag2^-/-/Fah^-/-/Aavr^-/- (TIRFA) mouse model overcoming this translational roadblock, by combining liver humanization with AAV receptor (AAVR) ablation, rendering murine cells impermissive to AAV transduction. Using human liver chimeric TIRFA mice, we demonstrate increased transduction of clinically used AAV serotypes in primary human hepatocytes compared to humanized mice with wild-type AAVR. Further, we demonstrate AAV transduction in human teratoma-derived primary cells and liver cancer tissue, displaying the

SUBMITTER: Barzi M 

PROVIDER: S-EPMC10912671 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature