AUTHOR=Hamilton Bradley A. , Wright J. Fraser TITLE=Challenges Posed by Immune Responses to AAV Vectors: Addressing Root Causes JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.675897 DOI=10.3389/fimmu.2021.675897 ISSN=1664-3224 ABSTRACT=

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.