Recombinant Sendai virus provides a highly efficient gene transfer into human cord blood-derived hematopoietic stem cells

Hematopoietic stem cells (HSCs) are a promising target for gene therapy, however, the low efficiencies of gene transfer using currently available vectors face practical limitations. We have recently developed a novel and efficient gene transfer agent, namely recombinant Sendai virus (SeV), and we have here characterized SeV-mediated gene transfer to human cord blood (CB) HSCs and primitive progenitor cells (PPC) using the jelly fish green fluorescent protein (GFP) gene. Even at a relatively low titer (10 multiplicity of infections), SeV achieved highly efficient GFP expression in CB CD34⁺ cells (85.5 ± 5.8%), as well as more immature CB progenitor cells, CD34⁺AC133⁺ (88.2 ± 3.7%) and CD34⁺CD38^- (84.6 ± 5.7%) cells, without cytokines prestimulation, that was a clear contrast to the features of gene transfer using retroviruses. SeV-mediated gene transfer was not seriously affected by the cell cycle status. In vitro cell differentiation studies revealed that gene transfer occurred in progenitor cells of all lineages (GM-CFU, 73.0 ± 11.1%; BFU-E, 24.7 ± 4.0%; Mix-CFU, 59 ± 4.0%; and total, 50.0 ± 7.0%). These findings show that SeV could prove to be a promising vector for efficient gene transfer to CB HSCs, while preserving their ability to reconstitute the entire hematopoietic series.