Influence of Pre-existing Anti-capsid Neutralizing and Binding Antibodies on AAV Vector Transduction.

ABSTRACT: Pre-existing immunity to adeno-associated virus (AAV) is highly prevalent in humans and can profoundly impact transduction efficiency. Despite the relevance to AAV-mediated gene transfer, relatively little is known about the fate of AAV vectors in the presence of neutralizing antibodies (NAbs). Similarly, the effect of binding antibodies (BAbs), with no detectable neutralizing activity, on AAV transduction is ill defined. Here, we delivered AAV8 vectors to mice carrying NAbs and demonstrated that AAV particles are taken up by both liver parenchymal and non-parenchymal cells; viral particles are then rapidly cleared, without resulting in transgene expression. In vitro, imaging of hepatocytes exposed to AAV vectors pre-incubated with either NAbs or BAbs revealed that virus is taken up by cel

SUBMITTER: Fitzpatrick Z 

PROVIDER: S-EPMC5948224 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature