ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Induction of shock after intravenous injection of adenovirus vectors: a critical role for platelet-activating factor.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Core polymer optimization of ternary siRNA nanoparticles enhances in vivo safety, pharmacokinetics, and tumor gene silencing.Biomaterials · 2023Article
- In Vivo Tracking for Oncolytic Adenovirus Interactions with Liver Cells.Biomedicines · 2022Article
- Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19.SN comprehensive clinical medicine · 2021Review
- Kupffer cell release of platelet activating factor drives dose limiting toxicities of nucleic acid nanocarriers.Biomaterials · 2021Article
- Innate immunity to adenovirus: lessons from mice.FEBS letters · 2019Review
- Gene-Therapeutic Strategies Targeting Angiogenesis in Peripheral Artery Disease.Medicines (Basel, Switzerland) · 2018Review
- And Then There Was Light: Perspectives of Optogenetics for Deep Brain Stimulation and Neuromodulation.Frontiers in neuroscience · 2017Review
- Challenges and Prospects for Helper-Dependent Adenoviral Vector-Mediated Gene Therapy.Biomedicines · 2014Review
- IL-1α and complement cooperate in triggering local neutrophilic inflammation in response to adenovirus and eliminating virus-containing cells.PLoS pathogens · 2014Article
- Intratumoral delivery of CD154 homolog (Ad-ISF35) induces tumor regression: analysis of vector biodistribution, persistence and gene expression.Cancer gene therapy · 2012Article
- Adenovirus-triggered innate signalling pathways.European journal of microbiology & immunology · 2011Review
- A novel pancreatropic coxsackievirus vector expressing glucagon-like peptide 1 reduces hyperglycemia in streptozotocin-treated mice.Journal of virology · 2011Article
- Helper-dependent adenoviral vectors for liver-directed gene therapy.Human molecular genetics · 2011Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Innate immune responses are a major barrier to safe systemic gene therapy with adenovirus (Ad) vectors. We show that intravenous (IV) injection of rats with Ad5 vectors causes a novel rapid shock reaction that involves hypotension, hemoconcentration, tissue edema, and vasocongestion, with notable pathology in the pancreas and the gastrointestinal system. We show for the first time that this reaction is dependent on platelet-activating factor (PAF), a lipid signaling molecule that is a known shock inducer. Ad upregulated PAF within 5 minutes in vivo, and antagonists of the PAF receptor were able to prevent Ad-induced shock. Ad upregulated PAF via the reticuloendothelial system (RES), because splenectomy or depletion of phagocytes blocked the ability of Ad to induce both PAF and shock. Rats were considerably more sensitive to Ad-induced shock than were mice, but PAF mediated shock in both species. Other Ad-induced innate immune responses such as cytokine induction and thrombocytopenia were not mediated by PAF. In summary, systemic IV injection of Ad stimulates the RES to upregulate PAF within a matter of minutes, which results in shock. The identification of this novel pathway suggests strategies to improve the safety of systemic gene therapy with Ad vectors.
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Registered trials
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