Abstract: Compositions and methods for depleting B cells and/or eliminating neutralizing antibodies, particularly for AA V gene therapy administration, are disclosed. Neutralizing alloantibodies (NAbs) to adeno-associated virus (AAV) occur both naturally after exposure to the wildtype circulating virus and following AAV vector mediated gene therapies. When pre-existing, these NAbs preclude eligibility to receive curative AAV gene therapy vectors. Following AAV infusion, the development of NAbs preclude re-administration even with other vector serotypes due to cross-reactivity. Given waning of transgene activity seen in multiple AAV gene therapy trials for hemophilia and the potential need to boost responses with growth in pediatric patients, the ability to re-administer AAV vectors is critical.