ArticleProceedings of the National Academy of Sciences of the United States of America1997
Insertion of the adenoviral E3 region into a recombinant viral vector prevents antiviral humoral and cellular immune responses and permits long-term gene expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
54 citing papers in PubMed, 202 citations in OpenAlex.
- Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study.The Lancet. Infectious diseases · 2013Trial
- Pilot trial of intravenous infusion of a replication-selective adenovirus (ONYX-015) in combination with chemotherapy or IL-2 treatment in refractory cancer patients.Cancer gene therapy · 2003Trial
- Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity.Gene therapy · 2001Trial
- Review
- Nonclinical characterization of ICVB-1042 as a selective oncolytic adenovirus for solid tumor treatment.Communications biology · 2024Article
- Adenoviral Vector System: A Comprehensive Overview of Constructions, Therapeutic Applications and Host Responses.Journal of microbiology (Seoul, Korea) · 2024Review
- Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5-based Constructs.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Liver-targeted gene therapy: Approaches and challenges.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2015Review
- Homologous recombination in E3 genes of human adenovirus species D.Journal of virology · 2013Article
- A novel hybrid adenoretroviral vector with more extensive E3 deletion extends transgene expression in submandibular glands.Human gene therapy methods · 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
- Review
- Article
- Verapamil enhances the antitumoral efficacy of oncolytic adenoviruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Lentivectors encoding immunosuppressive proteins genetically engineer pancreatic beta-cells to correct diabetes in allogeneic mice.Gene therapy · 2009Article
- Development of lentiviral vectors with regulated respiratory epithelial expression in vivo.American journal of respiratory cell and molecular biology · 2007Article
- Advances in prostate cancer immunotherapies.Drugs & aging · 2007Review
- Review
- Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Recombinant adenoviruses (Ads) are highly efficient at transferring foreign genes to the liver in vivo; however, the duration of gene expression is limited by the host antiviral immune response, which prevents expression upon readministration of the virus. To test whether overexpression of the immunomodulatory products of the early Ad genome region 3 (E3) could prevent the antiviral immune response and prolong expression of foreign genes delivered by Ad vectors, we injected a recombinant Ad (Ad-E3-hBUGT), containing both E3 and the human bilirubin-uridine-diphosphoglucuronate-glucuronosyltransferase (BUGT) genes, into BUGT-deficient hyperbilirubinemic Gunn rats. Control Gunn rats received Ad-hBUGT, which expresses human BUGT alone. An initial injection of either virus resulted in hepatic expression of human BUGT as evidenced by excretion of bilirubin glucuronides in bile and a reduction of mean serum bilirubin levels from 7.0 mg/dl to 1.9-2.7 mg/dl within 7 days. In Ad-E3-hBUGT-injected rats, serum bilirubin levels increased to 4.5 mg/dl by 84 days after infection, but a second administration of the virus on that day resulted in a hypobilirubinemic response similar to that seen with the first injection. In contrast, rats receiving Ad-hBUGT had serum bilirubin levels of 7 mg/dl on day 84 after infection, but showed no reduction of serum bilirubin by reinjection of the virus on that day. In the rats injected with Ad-E3-hBUGT, but not in the ones injected with Ad-hBUGT, there was a marked inhibition of the antiviral antibody and Ad-specific cytotoxic T lymphocyte responses. This is the first demonstration that insertion of E3 genes in recombinant Ads facilitates readministration of a functional vector for long-term correction of an inherited metabolic disorder.
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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.