ArticleProceedings of the National Academy of Sciences of the United States of America2011
Activation of the NF-kappaB pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 70 citations in OpenAlex.
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- Maggot extracts chemo-prevent inflammation and tumorigenesis accompanied by changes in the intestinal microbiome and metabolome in AOM/DSS-induced mice.Frontiers in microbiology · 2023Article
- Muscle regeneration affects Adeno Associated Virus 1 mediated transgene transcription.Scientific reports · 2022Article
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- Utilizing minimally purified secreted rAAV for rapid and cost-effective manipulation of gene expression in the CNS.Molecular neurodegeneration · 2020Article
- Morpholino-induced exon skipping stimulates cell-mediated and humoral responses to dystrophin in mdx mice.The Journal of pathology · 2019Article
- RFX1 and RFX3 Transcription Factors Interact with the D Sequence of Adeno-Associated Virus Inverted Terminal Repeat and Regulate AAV Transduction.Scientific reports · 2018Article
- Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial.Human gene therapy · 2017Review
- Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects.Journal of inherited metabolic disease · 2017Review
- Plasmacytoid and conventional dendritic cells cooperate in crosspriming AAV capsid-specific CD8Blood · 2017Article
- Central role of the TIR-domain-containing adaptor-inducing interferon-β (TRIF) adaptor protein in murine sterile liver injury.Hepatology (Baltimore, Md.) · 2017Article
- Optimized AAV rh.10 Vectors That Partially Evade Neutralizing Antibodies during Hepatic Gene Transfer.Frontiers in pharmacology · 2017Article
- Primate neural retina upregulates IL-6 and IL-10 in response to a herpes simplex vector suggesting the presence of a pro-/anti-inflammatory axis.Experimental eye research · 2016Article
- Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages.Acta biochimica et biophysica Sinica · 2016Article
- Adeno-Associated Virus: The Naturally Occurring Virus Versus the Recombinant Vector.Human gene therapy · 2016Article
- Microglia-specific targeting by novel capsid-modified AAV6 vectors.Molecular therapy. Methods & clinical development · 2016Article
- Copackaged AAV9 Vectors Promote Simultaneous Immune Tolerance and Phenotypic Correction of Pompe Disease.Human gene therapy · 2016Article
- Reprogramming Immune Response With Capsid-Optimized AAV6 Vectors for Immunotherapy of Cancer.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2015Article
- Role of capsid proteins in parvoviruses infection.Virology journal · 2015Review
Corrections and comments
- Retraction · 2017-12-20Duplication of Data · Duplication of/in Image · Falsification/Fabrication of Data ·
- Retracted
Authors and funding
7 authors at 4 institutions in 5 countries.
Funding
Abstract
Because our in silico analysis with a human transcription factor database demonstrated the presence of several binding sites for NF-κB, a central regulator of cellular immune and inflammatory responses, in the adeno-associated virus (AAV) genome, we investigated whether AAV uses NF-κB during its life cycle. We used small molecule modulators of NF-κB in HeLa cells transduced with recombinant AAV vectors. VP16, an NF-κB activator, augmented AAV vector-mediated transgene expression up to 25-fold. Of the two NF-κB inhibitors, Bay11, which blocks both the canonical and the alternative NF-κB pathways, totally ablated transgene expression, whereas pyrrolidone dithiocarbamate, which interferes with the classical NF-κB pathway, had no effect. Western blot analyses confirmed the abundance of the nuclear p52 protein component of the alternative NF-κB pathway in the presence of VP16, which was ablated by Bay11, suggesting that AAV transduction activates the alternative NF-κB pathway. In vivo, hepatic AAV gene transfer activated the canonical NF-κB pathway within 2 h, resulting in expression of proinflammatory cytokines and chemokines (likely reflecting the sensing of viral particles by antigen-presenting cells), whereas the alternative pathway was activated by 9 h. Bay11 effectively blocked activation of both pathways without interfering with long-term transgene expression while eliminating proinflammatory cytokine expression. These studies suggest that transient immunosuppression with NF-κB inhibitors before transduction with AAV vectors should lead to a dampened immune response, which has significant implications in the optimal use of AAV vectors in human gene therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.