Strategies to circumvent humoral immunity to adeno-associated viral vectors.

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.

Duke Scholars

Author Aravind Asokan Surgery, Surgical Sciences