Lentivirus-mediated globin gene transfer rescues Hbb

^th3/th3 hematopoietic chimeras from death. Donor Hbb^+/+, Hbb^th3/+, and Hbb^th3/th3 FLCs harvested from ED 14.5 embryos were transduced with TNS9 or a control lentivirus encoding the eGFP protein. Of the 13 TNS9-treated chimeras, 6 stably and predominantly expressed Hbb^hu (> 95% of total Hb). The asterisk indicates that healthy Hbb^+/+, Hbb^th3/+, and Hbb^th3/th3 FLCs recipient mice were killed at 4 or 6 months after transplantation to perform pathologic and molecular analysis (see “Results” and Table 1). The remaining mice were killed 8 months after transplantation to complete the analysis. Two mice died 4 months after transplantation, showing profound anemia. Measurement of vector copy number in bone marrow, spleen, and peripheral blood showed, respectively, undetectable and very low vector copy number, thus establishing that these 2 chimeras had been temporally rescued by genetically modified, short-lived erythroid progenitor cells.