Direct interaction of human serum proteins with AAV virions to enhance AAV transduction: immediate impact on clinical applications.

ABSTRACT: Recent hemophilia B clinical trials using adeno-associated virus (AAV) gene delivery have demonstrated much lower coagulation factor IX (FIX) production in patients compared with the high levels observed in animal models and AAV capsid-specific cytotoxic T lymphocyte response elicited at high doses of AAV vectors. These results emphasize the necessity to explore effective approaches for enhancement of AAV transduction. Initially, we found that incubation of all AAV vectors with human serum enhanced AAV transduction. Complementary analytical experiments demonstrated that human serum albumin (HSA) directly interacted with the AAV capsid and augmented AAV transduction. The enhanced transduction was observed with clinical grade HSA. Mechanistic studies suggest that HSA increases AAV binding to

SUBMITTER: Wang M 

PROVIDER: S-EPMC5269444 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature