Introduction: Recent success in gene therapy of certain monogenic diseases in the clinic has infused enthusiasm into the continued development of recombinant adeno-associated viral (AAV) vectors as next-generation biologics. However, progress in clinical trials has also highlighted the challenges posed by the host humoral immune response to AAV vectors. Specifically, while pre-existing neutralizing antibodies (NAbs) limit the cohort of eligible patients, NAb generation following treatment prevents vector re-dosing.
Areas covered: In this review, we discuss a spectrum of complementary strategies that can help circumvent the host humoral immune response to AAV.
Expert opinion: Specifically, we present a dual perspective, that is, vector versus host, and highlight the clinical attributes, potential caveats and limitations as well as complementarity associated with the various approaches.
Keywords: adeno-associated virus; capsid; humoral immune response; neutralizing antibody; recombinant adeno-associated viral vectors.