title: Adenovirus-platelet interaction in blood causes virus sequestration to the reticuloendothelial system of the liver.
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.
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Box 357720, Seattle, WA 98195, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stone
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Dmitry
authors.initials: D
authors.lastname: Shayakhmetov
authors.forename: Zong-Yi
authors.initials: ZY
authors.lastname: Li
authors.forename: Shaoheng
authors.initials: S
authors.lastname: Ni
authors.forename: André
authors.initials: A
authors.lastname: Lieber
mesh_terms: D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D012157:Mononuclear Phagocyte System / Q000821:virology*