Adenovirus Serotype 5 Hexon Mediates Liver Gene Transfer

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Adenovirus Serotype 5 Hexon Mediates Liver Gene Transfer

Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. However, targeting of liver cells by adenoviruses compromises their potential efficacy. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor (CAR) to bind cells. Paradoxically, following intravascular delivery, CAR is not used for liver transducti...

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Identification of Adenovirus Serotype 5 Hexon Regions

24 Most of an intravenous dose of species C adenovirus serotype 5 (Ad5) is 25 destroyed by liver Kupffer cells. In contrast, another species C virus, Ad6, evades these 26 cells to mediate more efficient liver gene delivery. Given that this difference in Kupffer 27 cell interaction is mediated by the hypervariable (HVR) loops of the virus hexon protein, 28 we genetically modified each of the sev...

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Neutralizing antibodies to adenovirus serotype 5 vaccine vectors are directed primarily against the adenovirus hexon protein.

The utility of recombinant adenovirus serotype 5 (rAd5) vector-based vaccines for HIV-1 and other pathogens will likely be limited by the high prevalence of pre-existing Ad5-specific neutralizing Abs (NAbs) in human populations. However, the immunodominant targets of Ad5-specific NAbs in humans remain poorly characterized. In this study, we assess the titers and primary determinants of Ad5-spec...

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Construction and characterization of adenovirus serotype 5 packaged by serotype 3 hexon.

Adenovirus serotype 5 (Ad5) has great potential for gene therapy applications. A major limitation, however, is the host immune response against Ad5 infection that often prevents the readministration of Ad5 vectors. In this regard, the most abundant capsid protein, hexon, has been implicated as the major target for neutralizing antibodies. In this study, we sought to escape the host neutralizati...

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Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo.

Human species C adenovirus serotype 5 (Ad5) is the most common viral vector used in clinical studies worldwide. Ad5 vectors infect liver cells in vivo with high efficiency via a poorly defined mechanism, which involves virus binding to vitamin K-dependent blood coagulation factors. Here, we report that the major Ad5 capsid protein, hexon, binds human coagulation factor X (FX) with an affinity o...

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ژورنال

عنوان ژورنال: Cell

سال: 2008

ISSN: 0092-8674

DOI: 10.1016/j.cell.2008.01.016