AUTHOR=Rogers Geoffrey L., Martino Ashley T., Aslanidi George V., Jayandharan Giridhara R., Srivastava Arun , Herzog Roland W.
TITLE=Innate Immune Responses to AAV Vectors
JOURNAL=Frontiers in Microbiology
VOLUME=2
YEAR=2011
URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2011.00194
DOI=10.3389/fmicb.2011.00194
ISSN=1664-302X
ABSTRACT=
Gene replacement therapy by in vivo delivery of adeno-associated virus (AAV) is attractive as a potential treatment for a variety of genetic disorders. However, while AAV has been used successfully in many models, other experiments in clinical trials and in animal models have been hampered by undesired responses from the immune system. Recent studies of AAV immunology have focused on the elimination of transgene-expressing cells by the adaptive immune system, yet the innate immune system also has a critical role, both in the initial response to the vector and in prompting a deleterious adaptive immune response. Responses to AAV vectors are primarily mediated by the TLR9–MyD88 pathway, which induces the production of pro-inflammatory cytokines by activating the NF-κB pathways and inducing type I IFN production; self-complementary AAV vectors enhance these inflammatory processes. Additionally, the alternative NF-κB pathway influences transgene expression in cells transduced by AAV. This review highlights these recent discoveries regarding innate immune responses to AAV and discusses strategies to ablate these potentially detrimental signaling pathways.