We have studied the regulation of the human β-globin gene after retroviral transfer into a variety of transformed and normal hematopoietic cells. After transfer into murine erythroleukemia cells (MEL) expression from the human β-globin gene responds to inducers of erythroid maturation in parallel to the endogenous murine globin genes. After infection of human BFU-E, RNA expression from the virally-transferred β-globin gene was measured at 2.5%-5% of the endogenous β-globin level. The most improved globin vectors can transfer the human β-globin gene into pluripotent hematopoietic stem cells in mouse bone marrow. Mice reconstituted with infected marrow show human β-globin RNA and protein expression in peripheral blood cells for over 4 months. In these animals, both myeloid and lymphoid cells carry the integrated provirus at a level of about 1 copy per cell. In serial transplantation experiments, bone marrow from these animals is capable or repopulating secondary and tertiary recipient animals which go on to show long-term human β-globin expression. Retroviral vectors thus provide a practical way to refine models of globin gene regulation through in vivo tests and to evaluate the feasibility of protocols for gene addition therapy.
CITATION STYLE
Gelinas, R. E., Bender, M. A., Miller, A. D., & Novak, U. (1990). Long-term expression of the human β-globin gene after retroviral transfer into pluripotent hematopoietic stem cells of the mouse. In Advances in Experimental Medicine and Biology (Vol. 271, pp. 135–148). https://doi.org/10.1007/978-1-4613-0623-8_15
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