ArticleGene therapy2006
Modulation of TNFalpha, a determinant of acute toxicity associated with systemic delivery of first-generation and helper-dependent adenoviral vectors.
Article in Gene therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- 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
- A Case of Acute Viral Pericarditis Complicated With Pericardial Effusion Induced by Third Dose of COVID Vaccination.Cureus · 2022Article
- Article
- High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.International journal of molecular sciences · 2020Review
- PEGylated helper-dependent adenoviral vector expressing human Apo A-I for gene therapy in LDLR-deficient mice.Gene therapy · 2013Article
- 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
- Combined cocaine hydrolase gene transfer and anti-cocaine vaccine synergistically block cocaine-induced locomotion.PloS one · 2012Article
- Hyperactive sleeping beauty transposase enables persistent phenotypic correction in mice and a canine model for hemophilia B.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Chimeric alphavirus vaccine candidates protect mice from intranasal challenge with western equine encephalitis virus.Vaccine · 2009Article
- Strategies to overcome host immunity to adenovirus vectors in vaccine development.Expert review of vaccines · 2009Review
- Immunization against the transgene but not the TetON switch reduces expression from gutless adenoviral vectors in the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2008Article
- Current advances and future challenges in Adenoviral vector biology and targeting.Current gene therapy · 2007Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Understanding the determinants of the host innate immune response to systemic administration of adenoviral (Ad) vectors is critical for clinical gene therapy. Acute toxicity occurs within minutes to hours after vector administration and is characterized by activation of innate immune responses. Our data indicate that in mice, indicators of vector toxicity include elevations of cytokine levels, liver transaminase levels and thrombocytopenia. To discern potential targets for blunting this host response, we evaluated genetic factors in the host response to systemically administered first-generation Ad vectors (FGV) and helper-dependent Ad vectors (HDV) containing beta-galactosidase expression cassettes. A preliminary screen for modulation of vector-induced thrombocytopenia revealed no role for interferon-gamma, mast cells or perforin. However, vector-induced thrombocytopenia and interleukin 6 (IL-6) expression are less evident in tumor necrosis factor alpha (TNFalpha)-deficient mice. Moreover, we also demonstrated that TNFalpha blockade via antibody or huTNFR:Fc pretreatment attenuates both thrombocytopenia (>40% increase in platelet count) and IL-6 expression (>80% reduction) without affecting interleukin 12 , liver enzymes, hematological indices or vector transduction in a murine model. Our data indicate that the use of HDV, in combination with clinically approved TNFalpha immunomodulation, may represent an approach for improving the therapeutic index of Ad gene therapy for human clinical trials.
Indexed as
Identifiers
What OpenQuestion holds
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.