ArticleHuman gene therapy2010
MyD88-dependent silencing of transgene expression during the innate and adaptive immune response to helper-dependent adenovirus.
Article in Human gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
The trial behind it
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
24 citing papers in PubMed, 34 citations in OpenAlex.
- Immunological pathogenesis and treatment progress of adenovirus pneumonia in children.Italian journal of pediatrics · 2025Review
- Additional expression of T-cell engager in clinically tested oncolytic adeno-immunotherapy redirects tumor-infiltrated, irrelevant T cells against cancer cells to enhance antitumor immunity.Journal for immunotherapy of cancer · 2024Article
- Role of homologous recombination/recombineering on human adenovirus genome engineering: Not the only but the most competent solution.Engineering microbiology · 2024Review
- Adenovirus vector-based vaccines as forefront approaches in fighting the battle against flaviviruses.Human vaccines & immunotherapeutics · 2022Review
- Cytokine Responses to Adenovirus and Adenovirus Vectors.Viruses · 2022Review
- Oncolytic adeno-immunotherapy modulates the immune system enabling CAR T-cells to cure pancreatic tumors.Communications biology · 2021Article
- High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.International journal of molecular sciences · 2020Review
- Components from the Human c-myb Transcriptional Regulation System Reactivate Epigenetically Repressed Transgenes.International journal of molecular sciences · 2020Article
- Innate immunity to adenovirus: lessons from mice.FEBS letters · 2019Review
- Global Screening of Antiviral Genes that Suppress Baculovirus Transgene Expression in Mammalian Cells.Molecular therapy. Methods & clinical development · 2017Article
- Role of MyD88 in adenovirus keratitis.Immunology and cell biology · 2017Article
- Kinome-level screening identifies inhibition of polo-like kinase-1 (PLK1) as a target for enhancing non-viral transgene expression.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Challenges and Prospects for Helper-Dependent Adenoviral Vector-Mediated Gene Therapy.Biomedicines · 2014Review
- Feasibility of Applying Helper-Dependent Adenoviral Vectors for Cancer Immunotherapy.Biomedicines · 2014Review
- Combinatorial treatment with oncolytic adenovirus and helper-dependent adenovirus augments adenoviral cancer gene therapy.Molecular therapy oncolytics · 2014Article
- Beyond Gene Delivery: Strategies to Engineer the Surfaces of Viral Vectors.Biomedicines · 2013Review
- The role of chromatin in adenoviral vector function.Viruses · 2013Review
- Differential type I interferon-dependent transgene silencing of helper-dependent adenoviral vs. adeno-associated viral vectors in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- An oncolytic adenovirus enhanced for toll-like receptor 9 stimulation increases antitumor immune responses and tumor clearance.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- The human adenovirus type 5 E1B 55 kDa protein obstructs inhibition of viral replication by type I interferon in normal human cells.PLoS pathogens · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the host innate immune response after systemic administration of adenoviral vectors constitutes a principal impediment to successful clinical gene replacement therapies. Although helper-dependent adenoviruses (HDAds) lack all viral functional genes, systemic administration of a high dose of HDAd still elicits a potent innate immune response in host animals. Toll-like receptors (TLRs) are innate receptors that sense microbial products and trigger the maturation of antigen-presenting cells and cytokine production via MyD88-dependent signaling (except TLR3). Here we show that mice lacking MyD88 exhibit a dramatic reduction in proinflammatory cytokines after intravenous injection of a high dose of HDAd, and show significantly reduced induction of the adaptive immune response when compared with wild-type and TLR2-deficient mice. Importantly, MyD88(-/-) mice also show significantly higher and longer sustained transgene expression than do wild-type mice. Chromatin immunoprecipitation studies using wild-type and MyD88-deficient primary mouse embryonic fibroblasts showed significant MyD88-dependent transcriptional silencing of the HDAd-encoded transgenes. Our results demonstrate that MyD88 signaling, activated by systemic delivery of HDAd, initiates an innate immune response that suppresses transgene expression at the transcriptional level before initiation of the adaptive immune response.
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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.