Hepatocyte-specific gene expression from integrated lentiviral vectors

The Journal of Gene Medicine
Kathryn L NashAndrew Ml Lever

Abstract

For many applications, efficient gene therapy will require long-term, organ-specific therapeutic gene expression. Lentiviral vectors based on HIV-1 are promising gene delivery vehicles due to their ability to integrate transgenes into non-dividing cells. Many experimental vectors express transgenes under the control of the cytomegalovirus (CMV) immediate-early gene promoter. Although this promoter directs strong gene expression in vitro, it may be shut off rapidly in vivo. This study explores the potential of HIV-1-based vectors to transduce hepatocytes and compares gene expression from different promoters in integrated vectors. HIV-1-based vector plasmids expressing the green fluorescent protein (GFP) under the control of the CMV promoter, the alpha-1 antitrypsin gene promoter or promoters derived from the hepatitis B virus (HBV) genome were used to compare expression in transfected and transduced cell lines. Hepatocyte cell lines differed strikingly in their transfectability. Transduction with replication-deficient HIV-1-based vector particles incorporating the different promoter elements was uniformly effective in hepatocyte and non-hepatocyte lines. However, in hepatocytes, only the CMV, alpha-1 antitrypsin and HBV core but...Continue Reading

Citations

Nov 27, 2007·Genome Biology·Hoi-Ping Mok, Andrew Ml Lever
Jan 1, 2008·International Journal of Nanomedicine·Miguel N CentellesJuan M Irache
Aug 24, 2010·World Journal of Gastroenterology : WJG·Hussein-M Atta
Jan 6, 2011·Expert Opinion on Biological Therapy·Luc J W van der LaanQiuwei Pan
Jan 22, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Joohee JungShun'ichi Kuroda
Feb 21, 2007·The Journal of Gene Medicine·Clare SeldenHumphrey Hodgson
May 13, 2008·Chemico-biological Interactions·Stephanie M ZamuleCurtis J Omiecinski
Feb 14, 2006·Virology·Meg M Laakso, Richard E Sutton
Sep 28, 2016·Expert Opinion on Drug Metabolism & Toxicology·M José Gómez-LechónM Teresa Donato
Mar 18, 2005·Gene Therapy·B SalaniL Varesio
Oct 27, 2006·Gene Therapy·K FosterJ G Dickson
Jun 23, 2018·Oncology Letters·Afiah Nasuha AznanZakiah Jubri

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