ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Redundant and synergistic mechanisms control the sequestration of blood-born adenovirus in the liver.
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 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Cell carriage, delivery, and selective replication of an oncolytic virus in tumor in patients.Science translational medicine · 2012Trial
- Oncolytic adenoviruses in bladder and kidney cancers: emerging strategies and next frontiers.Frontiers in microbiology · 2025Review
- Targeted, safe, and efficient gene delivery to human hematopoietic stem and progenitor cells in vivo using the engineered AVID adenovirus vector platform.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Innate immune surveillance of the circulation: A review on the removal of circulating virions from the bloodstream.PLoS pathogens · 2022Review
- Cytokine Responses to Adenovirus and Adenovirus Vectors.Viruses · 2022Review
- Adenovirus Type 6: Subtle Structural Distinctions from Adenovirus Type 5 Result in Essential Differences in Properties and Perspectives for Gene Therapy.Pharmaceutics · 2021Review
- A New Look at Vaccine Strategies Against PPRV Focused on Adenoviral Candidates.Frontiers in veterinary science · 2021Review
- Retargeting adenoviruses for therapeutic applications and vaccines.FEBS letters · 2020Review
- A New Gorilla Adenoviral Vector with Natural Lung Tropism Avoids Liver Toxicity and Is Amenable to Capsid Engineering and Vector Retargeting.Journal of virology · 2020Article
- Innate immunity to adenovirus: lessons from mice.FEBS letters · 2019Review
- Hexons from adenovirus serotypes 5 and 48 differentially protect adenovirus vectors from neutralization by mouse and human serum.PloS one · 2018Article
- Comparison of Liver Detargeting Strategies for Systemic Therapy with Oncolytic Adenovirus Serotype 5.Biomedicines · 2017Article
- Cryo-EM structure of human adenovirus D26 reveals the conservation of structural organization among human adenoviruses.Science advances · 2017Article
- Liver-resident CD103+ dendritic cells prime antiviral CD8+ T cells in situ.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Retargeted oncolytic adenovirus displaying a single variable domain of camelid heavy-chain-only antibody in a fiber protein.Molecular therapy oncolytics · 2015Article
- Challenges and Prospects for Helper-Dependent Adenoviral Vector-Mediated Gene Therapy.Biomedicines · 2014Review
- In vivo image analysis of BoHV-4-based vector in mice.PloS one · 2014Article
- A myeloid cell-binding adenovirus efficiently targets gene transfer to the lung and escapes liver tropism.Gene therapy · 2013Article
- Intravenous genetic mesothelin vaccine based on human adenovirus 40 inhibits growth and metastasis of pancreatic cancer.International journal of cancer · 2013Article
- FX and host defense evasion tactics by adenovirus.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Human adenovirus (Ad) is a ubiquitous pathogen causing a wide range of diseases. Although the interactions of human Ad serotype 5 (Ad5) with susceptible cells in vitro are known in great detail, host factors controlling the tissue specificity of Ad5 infection in vivo remain poorly understood. Here, we analyzed the mechanisms of sequestration by the liver for blood-born human Ads and Ad5-based vectors. Our data suggest that several known mechanisms that lead to Ad5 sequestration by the liver become engaged in a redundant, sequential, and synergistic manner to ensure the rapid clearance of circulating virus particles from the blood. These mechanisms include (i) trapping of the virus by liver residential macrophages, Kupffer cells; (ii) Ad5 hepatocyte infection via blood factor-hexon interactions; and (iii) Ad5 penton RGD motif-mediated interactions with liver endothelial cells and hepatocytes, mediating virus retention in the space of Disse. More important, we show that when all of these mechanisms are simultaneously inactivated via mutations of Ad5 capsid proteins and pharmacological interventions, virus sequestration by the liver is markedly reduced. Therefore, our study is the first demonstration of the principal possibility of ablating the sequestration of blood-born Ad in the liver via specific inactivation of a defined set of mechanisms that control this process.
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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.