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J Virol. 2007 May;81(9):4866-71. Epub 2007 Feb 14.

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

Author information

  • 1Division of Medical Genetics, Department of Medicine, University of Washington, Box 357720, Seattle, WA 98195, USA.

Abstract

Intravenous (i.v.) delivery of recombinant adenovirus serotype 5 (Ad5) 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.

PMID:
17301138
[PubMed - indexed for MEDLINE]
PMCID:
PMC1900148
Free PMC Article

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