Adenovirus-mediated gene transfer in the transplant setting: Part III. variables affecting gene transfer in liver grafts

Kenneth E. Drazan, Lily Wu, Xiu Da Shen, Debbie Bullington, Oded Jurim, Ronald W. Busuttil, Abraham Shared

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

We have established a system of efficient gene transfer to liver grafts using adenovirus vectors. The purpose of this study was to examine variables affecting gene transfer to rat liver grafts during cold preservation. Our results demonstrate that gene transfer efficiency was directly correlated with the ratio of vector to hepatic cells (multiplicity of infection [MOI]) and the length of exposure to the vector. At MOIs of 10:1 and 50:1, the hepatic cell transduction rate was 25-30% and 100%, respectively. However, higher MOI was associated with significant mortality. Prolonging the cold preservation/exposure time resulted in an increased transduction rate (50% at MOI of 10:1). Similar gene transfer efficiencies were observed when the vector was diluted in lactated Ringer’s or University of Wisconsin solution. Recombinant protein production was evident within 12 hr after reperfusion, and increased to a peak level within 48 hr. These results suggest a predictable pattern of gene transfer and expression after ex vivo transduction of liver grafts with adenovirus vectors. These data are essential in directing desirable levels of recombinant protein within the transplanted organ.

Original languageEnglish (US)
Pages (from-to)670-673
Number of pages4
JournalTransplantation
Volume59
Issue number5
DOIs
StatePublished - Mar 15 1995

ASJC Scopus subject areas

  • Transplantation

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