Efficient transduction and engraftment of G-CSF-mobilized peripheral blood CD34+ cells in nonhuman primates using GALV-pseudotyped gammaretroviral vectors

Molecular Therapy : the Journal of the American Society of Gene Therapy
Brian C BeardHans-Peter Kiem

Abstract

The optimal stem cell source for stem cell gene therapy has yet to be determined. Most large-animal studies have utilized peripheral blood or marrow-derived cells collected after administration of granulocyte colony-stimulating factor (G-SCF) and stem cell factor (SCF); however, SCF is unavailable for clinical use in the United States and the European Union. A recent study in a competitive repopulation assay in the rhesus macaque showed very inefficient marking of G-CSF-mobilized (G/only) peripheral blood (G-PBSC) CD34(+) cells relative to G-CSF and SCF-mobilized cells using vectors with an amphotropic pseudotype. Because G-PBSC would be the preferred target cell population for most clinical stem cell gene therapy applications, we asked whether we could achieve efficient transduction and engraftment of G-PBSC using Phoenix-GALV-pseudotyped vectors. We transplanted three baboons with G/only mobilized CD34(+) cells transduced with GALV-pseudotyped retroviral vectors. We observed high-level, persistent engraftment of gene-modified G-PBSC in all animals with gene marking levels in granulocytes up to 60%. We analyzed amphotropic (PIT2) and GALV (PIT1) receptor expression in G/only cells and found preferential expression of PIT1 afte...Continue Reading

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Citations

Aug 12, 2014·The Journal of Clinical Investigation·Jennifer E AdairHans-Peter Kiem
May 29, 2007·Blood·Bryan E ShepherdJanis L Abkowitz
May 11, 2012·Science Translational Medicine·Jennifer E AdairHans-Peter Kiem
Nov 19, 2011·Blood·Isabelle RivièreMichel Sadelain
Jun 18, 2014·Human Gene Therapy·Devikha ChandrasekaranThalia Papayannopoulou
Jun 17, 2010·The Journal of Clinical Investigation·Brian C BeardHans-Peter Kiem
Sep 14, 2019·Human Gene Therapy Methods·Driss BoudeffaOtto-Wilhelm Merten

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