Even a Worm Will Turn: Immunity Following AAV Vector Administration

While several approaches have been considered for in vivo delivery of therapeutic genes, vectors based on a small defective parvovirus, adeno-associated virus (AAV), have proven to be safer in achieving durable therapeutic transgene expression. Nevertheless, the use of vectors based on a virus that infects humans carries the risk of pre-existing host immunity from previous exposure to the virus. Even in the absence of prior infection, administration of large doses of a viral vector can activate host immune responses that can reduce, or prevent, therapeutic gene expression. Hence, careful monitoring of host immune responses before and after vector administration is required when delivering AAV-based gene therapies. Here we review anti-AAV immune responses and the approaches currently being explored to mitigate host immunity and achieve successful therapeutic gene expression.