Chapter title |
Long-term expression of the human beta-globin gene after retroviral transfer into pluripotent hematopoietic stem cells of the mouse.
|
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Chapter number | 15 |
Book title |
Molecular Biology of Erythropoiesis
|
Published in |
Advances in experimental medicine and biology, January 1989
|
DOI | 10.1007/978-1-4613-0623-8_15 |
Pubmed ID | |
Book ISBNs |
978-1-4612-7897-9, 978-1-4613-0623-8
|
Authors |
Gelinas, R E, Bender, M A, Miller, A D, Novak, U, Gelinas, Richard E., Bender, Michael A., Miller, A. Dusty, Novak, Ulrike |
Abstract |
We have studied the regulation of the human beta-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 beta-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 beta-globin gene was measured at 2.5%-5% of the endogenous beta-globin level. The most improved globin vectors can transfer the human beta-globin gene into pluripotent hematopoietic stem cells in mouse bone marrow. Mice reconstituted with infected marrow show human beta-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 of repopulating secondary and tertiary recipient animals which go on to show long-term human beta-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. |
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Professor > Associate Professor | 1 | 13% |
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Unknown | 1 | 13% |
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Unknown | 3 | 38% |