ArticlePloS one2013
IL12-mediated liver inflammation reduces the formation of AAV transcriptionally active forms but has no effect over preexisting AAV transgene expression.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 22 citations in OpenAlex.
- Tumor-specific AAV delivery of interleukin-12 enhances antitumor immunity and safety in ovarian cancer xenograft mouse model.Molecular therapy. Oncology · 2025Article
- Incomplete elimination of viral genomes is associated with chronic inflammation in nonhuman primate livers after AAV-mediated gene transfer.Gene therapy · 2025Article
- IL-15-producing splenic B cells play pathogenic roles in the development of autoimmune hepatitis.JHEP reports : innovation in hepatology · 2023Article
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- Article
- Lactobacillus rhamnosus GG Ameliorates Liver Injury and Hypoxic Hepatitis in Rat Model of CLP-Induced Sepsis.Digestive diseases and sciences · 2019Article
- Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity.Disease models & mechanisms · 2019Article
- Development of a liver-specific Tet-off AAV8 vector for improved safety of insulin gene therapy for diabetes.The journal of gene medicine · 2019Article
- Exposure to wild-type AAV drives distinct capsid immunity profiles in humans.The Journal of clinical investigation · 2018Article
- Advances in the mechanisms of action of cancer-targeting oncolytic viruses.Oncology letters · 2018Article
- Prevalent role of the insulin receptor isoform A in the regulation of hepatic glycogen metabolism in hepatocytes and in mice.Diabetologia · 2016Article
- Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice.Disease models & mechanisms · 2016Article
- Complementary Effects of Interleukin-15 and Alpha Interferon Induce Immunity in Hepatitis B Virus Transgenic Mice.Journal of virology · 2016Article
- Splicing regulator SLU7 is essential for maintaining liver homeostasis.The Journal of clinical investigation · 2014Article
- Role of the vector genome and underlying factor IX mutation in immune responses to AAV gene therapy for hemophilia B.Journal of translational medicine · 2014Article
- Pre-Clinical Assessment of Immune Responses to Adeno-Associated Virus (AAV) Vectors.Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant adenoassociated viral vectors (rAAV) have proven to be excellent candidates for gene therapy clinical applications. Recent results showed that cellular immunity to AAV represents a major challenge facing the clinical use of systemic administration of these vectors. Interestingly, no preclinical animal model has previously fully reproduced the clinical findings. The aim of the present work was to enhance the T cell immune response against AAV capsid in mice by the administration of a rAAV expressing the immunostimulatory cytokine IL-12. Our results indicate that although IL-12 expression enhanced the AAV capsid-specific immune response it failed to eliminate transduced hepatocytes and long-term expression was achieved. We found that AAV-mediated transgene expression is altered by IL-12-induced liver inflammation. However, IL-12 expression has no effect over preexisting AAV-mediated transgene expression. IL-12 down-regulates AAV mediated transgene expression via induction of IFN-γ production by NK and T cells, but without altering the transduction efficiency measured by viral genomes. Our results indicate that liver inflammation affects the formation of transcriptionally active AAV vector genomes through an unknown mechanism that can be avoided by the use of DNA-demethylating or anti-inflammatory agents.
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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.