Journal
JOURNAL OF VIROLOGY
Volume 81, Issue 9, Pages 4866-4871Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.02819-06
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Funding
- NCI NIH HHS [CA 080192, R01 CA080192] Funding Source: Medline
- NIAID NIH HHS [HL/AI 078836] Funding Source: Medline
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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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