Innate Immune Responses to AAV Vectors
Open Access
- 1 January 2011
- journal article
- Published by Frontiers Media SA in Frontiers in Microbiology
- Vol. 2, 194
- https://doi.org/10.3389/fmicb.2011.00194
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.Keywords
This publication has 67 references indexed in Scilit:
- Use of DAF-Displaying Adenovirus Vectors Reduces Induction of Transgene- and Vector-Specific Adaptive Immune Responses in MiceHuman Gene Therapy, 2011
- Preclinical and clinical progress in hemophilia gene therapyCurrent Opinion in Hematology, 2010
- Tolerance Induction to Cytoplasmic β-Galactosidase by Hepatic AAV Gene Transfer — Implications for Antigen Presentation and ImmunotoxicityPLOS ONE, 2009
- Transient Pretreatment With Glucocorticoid Ablates Innate Toxicity of Systemically Delivered Adenoviral Vectors Without Reducing EfficacyMolecular Therapy, 2009
- A critical role for direct TLR2-MyD88 signaling in CD8 T-cell clonal expansion and memory formation following vaccinia viral infectionBlood, 2009
- Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapyBlood, 2009
- Adenovirus Vector-Induced Innate Inflammatory Mediators, MAPK Signaling, As Well As Adaptive Immune Responses Are Dependent upon Both TLR2 and TLR9 In VivoThe Journal of Immunology, 2008
- Dendritic Cells Require the NF-κB2 Pathway for Cross-Presentation of Soluble AntigensThe Journal of Immunology, 2008
- The parvovirus capsid odyssey: from the cell surface to the nucleusTrends in Microbiology, 2008
- Differential Activation of Innate Immune Responses by Adenovirus and Adeno-Associated Virus VectorsJournal of Virology, 2002