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Journal of Virology, May 2007, p. 4866-4871, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02819-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Adenovirus-Platelet Interaction in Blood Causes Virus Sequestration to the Reticuloendothelial System of the Liver{triangledown}

Daniel Stone,1 Ying Liu,1 Dmitry Shayakhmetov,1 Zong-Yi Li,1 Shaoheng Ni,1 and André Lieber1,2*

Division of Medical Genetics, Department of Medicine,1 Department of Pathology, University of Washington, Seattle, Washington 981952

Received 20 December 2006/ Accepted 7 February 2007

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.

* Corresponding author. Mailing address: Division of Medical Genetics, University of Washington, Box 357720, Seattle, WA 98195. Phone: (206) 221-3973. Fax: (206) 685-8675. E-mail: lieber00{at}u.washington.edu

{triangledown} Published ahead of print on 14 February 2007.

Journal of Virology, May 2007, p. 4866-4871, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02819-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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