期刊
JOURNAL OF VIROLOGY
卷 83, 期 1, 页码 479-483出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01878-08
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资金
- Biotechnology and Biological Sciences Research Council
- British Heart Foundation
- European Union
- Caledonian Research Foundation
- Philip Gray Memorial Fellowship
- Katharine Dormandy Trust
- Garfield Weston Foundation
- BBSRC [BB/E021301/1, BB/E02145X/1, BB/E02145X/2] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E02145X/2, BB/E02145X/1, BB/E021301/1] Funding Source: researchfish
The deployment of adenovirus serotype 5 (Ad5)-based vectors is hampered by preexisting immunity. When such vectors are delivered intravenously, hepatocyte transduction is mediated by the hexon-coagulation factor X (FX) interaction. Here, we demonstrate that human sera efficiently block FX-mediated cellular binding and transduction of Ad5-based vectors in vitro. Neutralizing activity correlated well with the ability to inhibit Ad5-mediated liver transduction, suggesting that prescreening patient sera in this manner accurately predicts the efficacy of Ad5-based gene therapies. Neutralization in vitro can be partially bypassed by pseudotyping with Ad45 fiber protein, indicating that a proportion of neutralizing antibodies are directed against the Ad5 fiber.
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