Challenges Posed by Immune Responses to AAV Vectors: Addressing Root Causes.

Host immune responses that limit durable therapeutic gene expression and cause clinically significant inflammation remain a major barrier to broadly successful development of adeno-associated virus (AAV)-based human gene therapies. In this article, mechanisms of humoral and cellular immune responses to the viral vector are discussed. A perspective is provided that removal of pathogen-associated molecular patterns in AAV vector genomes to prevent the generation of innate immune danger signals following administration is a key strategy to overcome immunological barriers.
Competing Interests: JFW is a co-founder of Spark Therapeutics and Kriya Therapeutics, consults to companies developing rAAV-based gene therapy products, and is inventor of patents relating to recombinant viral vector design and manufacture. BAH declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Hamilton and Wright.)