Adenovirus-platelet interaction in blood causes virus sequestration to the reticuloendothelial system of the liver

被引：131

作者：

Stone, Daniel

Liu, Ying

Shayakhmetov, Dmitry

Li, Zong-Yi

Ni, Shaoheng

Lieber, Andre

机构：

[1] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA

[2] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

来源：

JOURNAL OF VIROLOGY | 2007年 / 81卷 / 09期

关键词：

D O I：

10.1128/JVI.02819-06

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Intravenous (i.v.) delivery of recombinant adenovirus serotype 5 (AM) vectors for gene therapy is hindered by safety and efficacy problems. We have discovered a new pathway involved in unspecific Ad5 sequestration and degradation. After i.v. administration, Ad5 rapidly binds to circulating platelets, which causes their activation/aggregation and subsequent entrapment in liver sinusoids. Virus-platelet aggregates are taken up by Kupffer cells and degraded. Ad sequestration in organs can be reduced by platelet depletion prior to vector injection. Identification of this new sequestration mechanism and construction of vectors that avoid it could improve levels of target cell transduction at lower vector doses.

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页码：4866 / 4871

页数：6

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