ArticleGene therapy2010
An ex vivo loop system models the toxicity and efficacy of PEGylated and unmodified adenovirus serotype 5 in whole human blood.
Article in Gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 38 citations in OpenAlex.
- Current use of pre-clinical models for evaluation of human adenovirus-based cancer therapeutics.Molecular therapy. Oncology · 2026Review
- Extracellular vesicles as missiles for enhanced anti-tumor efficacy of oncolytic viruses: from disseminating oncolysis and anti-tumor immunity to targeted delivery.Cell communication and signaling : CCS · 2025Review
- Cerebral venous thrombosis after COVID-19 vaccination: is the risk of thrombosis increased by intravascular application of the vaccine?Infection · 2021Article
- Boosting CAR T-cell responses in lymphoma by simultaneous targeting of CD40/4-1BB using oncolytic viral gene therapy.Cancer immunology, immunotherapy : CII · 2021Article
- Immunostimulatory oncolytic virotherapy for multiple myeloma targeting 4-1BB and/or CD40.Cancer gene therapy · 2020Article
- Retargeting adenoviruses for therapeutic applications and vaccines.FEBS letters · 2020Review
- Article
- One-Vector System for Multiplexed CRISPR/Cas9 against Hepatitis B Virus cccDNA Utilizing High-Capacity Adenoviral Vectors.Molecular therapy. Nucleic acids · 2018Article
- pH-sensitive oncolytic adenovirus hybrid targeting acidic tumor microenvironment and angiogenesis.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Human coagulation factor X-adenovirus type 5 complexes poorly stimulate an innate immune response in human mononuclear phagocytes.Journal of virology · 2015Article
- Enhanced tumor uptake and penetration of virotherapy using polymer stealthing and focused ultrasound.Journal of the National Cancer Institute · 2013Article
- Recent developments in oncolytic adenovirus-based immunotherapeutic agents for use against metastatic cancers.Cancer gene therapy · 2013Review
- Rapamycin enhances adenovirus-mediated cancer imaging and therapy in pre-immunized murine hosts.PloS one · 2013Article
- Optimizing adenoviral transduction of endothelial cells under flow conditions.Pharmaceutical research · 2012Article
- Complement activation and cell uptake responses toward polymer-functionalized protein nanocapsules.Biomacromolecules · 2012Article
- Adenovirus with hexon Tat-protein transduction domain modification exhibits increased therapeutic effect in experimental neuroblastoma and neuroendocrine tumors.Journal of virology · 2011Article
- Oncolytic adenovirus modified with somatostatin motifs for selective infection of neuroendocrine tumor cells.Gene therapy · 2011Article
- Advances and future challenges in adenoviral vector pharmacology and targeting.Current gene therapy · 2011Review
- Mutation of herpesvirus Saimiri ORF51 glycoprotein specifically targets infectivity to hepatocellular carcinoma cell lines.Journal of biomedicine & biotechnology · 2011Article
- Modifications of adenovirus hexon allow for either hepatocyte detargeting or targeting with potential evasion from Kupffer cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyethylene glycol coating (PEGylation) of adenovirus serotype 5 (Ad5) has been shown to effectively reduce immunogenicity and increase circulation time of intravenously administered virus in mouse models. Herein, we monitored clot formation, complement activation, cytokine release and blood cell association upon addition of uncoated or PEGylated Ad5 to human whole blood. We used a novel blood loop model where human blood from healthy donors was mixed with virus and incubated in heparin-coated PVC tubing while rotating at 37 degrees C for up to 8 h. Production of the complement components C3a and C5a and the cytokines IL-8, RANTES and MCP-1 was significantly lower with 20K-PEGylated Ad5 than with uncoated Ad5. PEGylation prevented clotting and reduced Ad5 binding to blood cells in blood with low ability to neutralize Ad5. The effect was particularly pronounced in monocytes, granulocytes, B-cells and T-cells, but could also be observed in erythrocytes and platelets. In conclusion, PEGylation of Ad5 can reduce the immune response mounted in human blood, although the protective effects are rather modest in contrast to published mouse data. Our findings underline the importance of developing reliable models and we propose the use of human whole blood models in pre-clinical screening of gene therapy vectors.
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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.