Retrovirus-mediated gene expression in hematopoietic cells correlates inversely with growth factor stimulation

Human Gene Therapy
M LuA D Ho

Abstract

Cells of the hematopoetic system, especially hematopoietic progenitor and stem cells, are perceived as ideal targets for human gene therapy. In this report, the stability of retrovirus-mediated gene expression driven by three different potent promoters has been examined in purified human CD34+ cells. The promoters, murine stem cell virus (MSCV) long terminal repeat (LTR) and pgk, show gene expression in 10 times more hematopoietic colonies derived from CD34+ cells than the commonly used Moloney murine leukemia virus (Mo-MLV) LTR. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis, however, demonstrates that the levels of gene expression in retrovirus-transduced cells decrease with time in long-term bone marrow cultures and in suspension cultures containing hematopoietic growth factors. Removal of hematopoietic growth factors from the suspension culture medium was associated with a decrease in cell proliferation and differentiation, but with stable gene expression. Retrovirus-mediated gene expression is, therefore, inversely related to proliferation and differentiation of the transduced CD34+ cells. These observations may have implications in future design and implementation of human gene therapy prot...Continue Reading

References

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Citations

Jan 28, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Perry B HackettLaurence J N Cooper
Jan 15, 2013·Translational Research : the Journal of Laboratory and Clinical Medicine·Perry B HackettLaurence J N Cooper
Jul 17, 2007·Seminars in Hematology·Robert Möhle, Lothar Kanz

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