Gene therapy targeting peripheral blood CD34+ hematopoietic stem cells of HIV-infected individuals

Human Gene Therapy
A GervaixF Wong-Staal

Abstract

Gene therapy is a promising treatment modality for acquired immunodeficiency syndrome (AIDS). Autologous transplantation with genetically altered pluripotent hematopoietic stem cells encoding anti-human immunodeficiency virus (HIV) genes could in theory completely and permanently reconstitute all blood lineages and immune functions with cells resistant to HIV. Recent studies showed that CD34+ stem cell can be mobilized in HIV-infected individuals after granulocyte colony-stimulating factor (G-CSF) administration without major side effects or increase of viral load. In this study, peripheral blood CD34+ cells of five HIV-infected individuals were mobilized with G-CSF and after leukapheresis and enrichment, subjected to retroviral transduction with genes encoding anti-HIV ribozyme-decoy fusion molecules. These cells were tested for the ability to give rise to progeny cells, for retroviral transduction efficiency, and for expression of the transgene. CD34+-derived macrophage-like cells were also challenged with HIV. Results showed that CD34+ cells from HIV-infected individuals gave rise to similar numbers of progeny colonies as cells from healthy donors. The transduction efficiency of these cells varied from 68.8 to 100% as assess...Continue Reading

References

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Citations

Oct 18, 2000·Advanced Drug Delivery Reviews·J J Rossi
Nov 20, 1998·Current Opinion in Biotechnology·P J WelchF Wong-Staal
Oct 13, 2000·Progress in Retinal and Eye Research·W W Hauswirth, A S Lewin
Dec 12, 2001·HIV Medicine·N Dorman, A M Lever
Dec 3, 2005·Hematology·Kevin MorrisLaurence J N Cooper
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Mar 16, 2002·Gene Therapy·G PalùF Manca
Jan 7, 2006·Gene Therapy·K V Morris, J J Rossi
Mar 15, 2000·Journal of Molecular Biology·M J Fedor

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