In vitro and ex vivo delivery of short hairpin RNAs for control of hepatitis C viral transcript expression

Bonnie E. Lonze, Horatio T. Holzer, Matthew K. Knabel, Jayme E. Locke, Gregory A. DiCamillo, Sunil S. Karhadkar, Robert A. Montgomery, Zhaoli Sun, Daniel S. Warren, Andrew M. Cameron

Research output: Contribution to journalArticle

Abstract

Recurrent hepatitis C virus (HCV) infection is the most common cause of graft loss and patient death after transplantation for HCV cirrhosis. Transplant surgeons have access to uninfected explanted livers before transplantation and an opportunity to deliver RNA interference-based protective gene therapy to uninfected grafts. Conserved HCV sequences were used to design short interfering RNAs and test their ability to knockdown HCV transcript expression in an in vitro model, both by transfection and when delivered via an adeno-associated viral vector. In a rodent model of liver transplantation, portal venous perfusion of explanted grafts with an adeno-associated viral vector before transplantation produced detectable short hairpin RNA transcript expression after transplantation. The ability to deliver anti-HCV short hairpin RNAs to uninfected livers before transplantation and subsequent exposure to HCV offers hope for the possibility of preventing the currently inevitable subsequent infection of liver grafts with HCV.

Original languageEnglish (US)
Pages (from-to)384-387
Number of pages4
JournalArchives of surgery
Volume147
Issue number4
DOIs
StatePublished - Apr 1 2012

ASJC Scopus subject areas

  • Surgery

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    Lonze, B. E., Holzer, H. T., Knabel, M. K., Locke, J. E., DiCamillo, G. A., Karhadkar, S. S., Montgomery, R. A., Sun, Z., Warren, D. S., & Cameron, A. M. (2012). In vitro and ex vivo delivery of short hairpin RNAs for control of hepatitis C viral transcript expression. Archives of surgery, 147(4), 384-387. https://doi.org/10.1001/archsurg.2011.1250