Envelope fusion protein binding studies in an inducible model of retrovirus receptor expression and in CD34(+) cells emphasize limited transduction at low receptor levels

Gene Therapy
P KurreH P Kiem

Abstract

Successful gene therapy for the treatment of heritable or acquired diseases typically requires high efficiency gene transfer and sustained transgene expression. Indirect evidence on the basis of RNA analysis and in vivo competitive repopulation experiments in animal models suggests a correlation between transduction efficiency and the abundance of retrovirus receptors on the hematopoietic target cell. However, transduction by oncoretroviral vectors is also subject to other factors such as target cell cycle status and the composition of the virus-containing medium, making it difficult to determine the level of receptor expression required for efficient transduction. In the present study we investigated the impact of receptor expression level on transduction by a vector with a gibbon ape leukemia virus (GALV) envelope protein in a tetracycline-inducible tissue culture model that allowed for the cell cycle-independent, regulated expression of the GALV receptor (Pit1) in otherwise non-susceptible NIH 3T3 cells. Up-regulation of receptor RNA expression by 4.5-fold resulted in a mean 150-fold increase in transduction efficiency. We then analyzed cell surface expression of the Pit1 receptor using a fusion protein consisting of GALV SU...Continue Reading

References

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Citations

Jan 5, 2006·Human Gene Therapy·Grant TrobridgeHans-Peter Kiem
Sep 17, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Thomas RelanderJohan Richter
Feb 5, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tobias NeffHans-Peter Kiem
Sep 1, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Peter A HornHans-Peter Kiem
Feb 28, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hideki HanawaArthur W Nienhuis
Oct 31, 2007·Biotechnology and Bioengineering·Natalia Landázuri, Joseph M Le Doux

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