ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Transient pretreatment with glucocorticoid ablates innate toxicity of systemically delivered adenoviral vectors without reducing efficacy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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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
65 citing papers in PubMed, 94 citations in OpenAlex.
- Immune reactivity after adenoviral-mediated aquaporin-1 cDNA transfer to human parotid glands.Oral diseases · 2017Trial
- High-capacity adenoviral vector-mediated expression of an LDLR/transferrin chimeric protein in muscle reduces atherosclerosis in LdlrMolecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Adenoviral-mediated gene transfer into the scala media of the mouse cochlea in vivo.bioRxiv : the preprint server for biology · 2026Article
- The RLR intrinsic antiviral system is expressed in neural retina and restricts lentiviral transduction of human Mueller cells.Experimental eye research · 2023Article
- Innate Immune Response to Viral Vectors in Gene Therapy.Viruses · 2023Review
- Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity.Nature communications · 2022Article
- A chitosan-mediated inhalable nanovaccine against SARS-CoV-2.Nano research · 2022Article
- Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy.Cell & bioscience · 2021Review
- Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis, Characterization, and Evaluation.International journal of molecular sciences · 2021Article
- In Vivo HSC Gene Therapy Using a Bi-modular HDAd5/35++ Vector Cures Sickle Cell Disease in a Mouse Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Effects of Short-Term Corticosteroid Use on Reactogenicity and Immunogenicity of the First Dose of ChAdOx1 nCoV-19 Vaccine.Frontiers in immunology · 2021Article
- Overcoming Immunological Challenges to Helper-Dependent Adenoviral Vector-Mediated Long-TermGenes · 2020Article
- Design of a MUC1-based tricomponent vaccine adjuvanted with FSL-1 for cancer immunotherapy.MedChemComm · 2019Article
- Modulation of immune responses in lentiviral vector-mediated gene transfer.Cellular immunology · 2019Review
- Optimization of Dexamethasone Administration for Maintaining Global Transduction Efficacy of Adeno-Associated Virus Serotype 9.Human gene therapy · 2019Article
- In vivo hematopoietic stem cell gene therapy ameliorates murine thalassemia intermedia.The Journal of clinical investigation · 2019Article
- Article
- Current and Future Treatments for Lysosomal Storage Disorders.Current treatment options in neurology · 2017Review
- In Vivo Hematopoietic Stem Cell Transduction.Hematology/oncology clinics of North America · 2017Review
- Neonatal Gene Therapy for Hemophilia B by a Novel Adenovirus Vector Showing Reduced Leaky Expression of Viral Genes.Molecular therapy. Methods & clinical development · 2017Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
More than 300 human clinical trials utilize recombinant adenoviruses (rAds) as a gene transfer vector, confirming that rAds continue to be of high clinical interest. A primary weakness of rAds is their known propensity to trigger an innate, proinflammatory immune response rapidly after high-dose, systemic administration. In this study, we investigated what affects that pre-emptive treatment with anti-inflammatory glucocorticoids might have upon Ad vector-triggered inflammatory immune responses. We found that a simple pretreatment regimen with Dexamethasone (DEX) can significantly reduce most Ad-induced innate immune responses. DEX prevented rAd induction of systemic cytokine/chemokine releases in a dose-dependent fashion, with higher dosages preventing rAd induction of acute thrombocytopenia, endothelial cell activation, proinflammatory gene induction, and leukocyte infiltration into transduced organs. Transient glucocorticoid pretreatment also significantly reduced rAd-induced adaptive immune responses, including a decreased induction of Ad-neutralizing antibodies (NAbs). Importantly, use of DEX did not reduce the efficacy of rAd-mediated gene transduction nor rAd-derived transgene expression. Our results demonstrate that a simple, pre-emptive and transient glucocorticoid pretreatment is a viable approach to reduce rAd-associated acute toxicities that currently limit the use of Ad vectors in systemic clinical applications.
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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.