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Adeno-associated virus (AAV) vectors are currently being tested not only in small animal models such as mice but also in large animal models, including pigs, dogs, and horses. Natural exposure to AAV occurs in most of the species used in these studies and potentially elicits a neutralizing humoral immune response to AAV. In this study, we show the prevalence of neutralizing antibodies (NAbs) to several AAV serotypes in these large animals as measured by an in vitro NAb assay and the ability of these NAbs to block AAV transduction in an in vivo mouse model of NAb passive transfer assay. The results of this study clearly show the importance of evaluating large animal models for the presence of AAV NAbs before enrolling them in AAV-mediated gene therapy studies.

human gene therapy, part b. methods/human gene therapy. part b. methods

Preexisting Neutralizing Antibodies to Adeno-Associated Virus Capsids in Large Animals Other Than Monkeys May Confound <i>In Vivo</i> Gene Therapy Studies

Preexisting Neutralizing Antibodies to Adeno-Associated Virus Capsids in Large Animals Other Than Monkeys May Confound In Vivo Gene Therapy Studies