Pre-existing immunity to recombinant adeno-associated viral (AAV) vectors has been a major hindrance to vector dosing and re-administration, which may be required to ensure the durability and long-term efficacy of gene therapy for some diseases. Eliminating neutralizing antibodies against different AAV serotypes that arise from prior exposure could enable effective gene transfer and avoid the problems inherent with pre-existing antibodies. In this pilot study, the PI proposes to assess the ability of a rapid antibody clearing agent (ACA) (cysteine protease) to diminish pre-existing humoral immunity to AAV capsids and determine if this approach could enable AAV vector administration in young seropositive rhesus monkeys. If successful, the proposed approach could potentially expand patient recruitment in gene therapy clinical trials and also increase the availability of nonhuman primates for preclinical studies.