Highly efficient gene transfer into cord blood nonobese diabetic/severe combined immunodeficiency repopulating cells by oncoretroviral vector particles pseudotyped with the feline endogenous retrovirus (RD114) envelope protein

Limited expression of the amphotropic envelope receptor is a recognized bar rier to efficient oncoretroviral vector-mediated gene transfer. Human hemat opoietic cell lines and cord blood-derived CD34(+) and CD34(+), CD38(-) cel l populations and the progenitors contained therein were transduced far mor e efficiently with oncoretroviral particles pseudotyped with the envelope p rotein of feline endogenous virus (RD114) than with conventional amphotropi c vector particles. Similarly, human repopulating cells from umbilical cord blood capable of establishing hematopoiesis in immunodeficient mice were e fficiently transduced with RD114-pseudotyped particles, whereas amphotropic particles were ineffective at introducing the proviral genome. After only a single exposure of CD34(+) cord blood cells to RD114-pseudotyped particle s, all engrafted nonobese diabetic/ severe combined immunodeficiency mice ( 15 of 15) contained genetically modified human bone marrow cells. Human cel ls that were positive for enhanced green fluorescent protein represented as much as 90% of the graft. The use of RD114-pseudotyped vectors may be adva ntageous for therapeutic gene transfer into hematopoietic stem cells. (Bloo d, 2000; 96:1206-1214) (C) 2000 by The American Society of Hematology.