Recombinant adeno-associated virus (AAV) is a promising delivery vehicle for in vivo gene therapy and has been widely tested in preclinical and clinical studies. However, despite the vast promise they hold for gene therapy, debilitating immune responses have been reported against the AAV capsid itself and/or to the transgene product. As a result of high vector doses, serious adverse effects like complement activation and liver toxicity have been observed, even leading to fatality of subjects in certain clinical trials. Although many of these adverse events can be managed with immunosuppressants, this is not true for all trial participants.