Adenovirus-Platelet Interaction in Blood Causes Virus Sequestration to the Reticuloendothelial System of the Liver-Reference-Cited by-同舟云学术

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

Published:2007-05 Issue:9 Volume:81 Page:4866-4871
ISSN:0022-538X
Container-title:Journal of Virology
language:en
Short-container-title:J Virol

Author:

Stone Daniel¹,Liu Ying¹,Shayakhmetov Dmitry¹,Li Zong-Yi¹,Ni Shaoheng¹,Lieber André¹²

Affiliation:

1. Division of Medical Genetics, Department of Medicine

2. Department of Pathology, University of Washington, Seattle, Washington 98195

Abstract

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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/JVI.02819-06

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