In utero gene transfer and expression: a sheep transplantation model |
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Authors: | Kantoff PW; Flake AW; Eglitis MA; Scharf S; Bond S; Gilboa E; Erlich H; Harrison MR; Zanjani ED; Anderson WF |
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Institution: | Laboratory of Molecular Hematology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892. |
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Abstract: | Retroviral-mediated gene transfer was used to insert a Neo R gene into fetal sheep hematopoietic cells obtained by exchange transfusion from lambs in utero. After gene transfer the cells were returned to the donor fetus. The lambs were examined after birth for the presence of a functioning Neo R gene. Of ten analyzable animals, six were positive for G418 resistant progenitor cells (CFU-Mix, CFU-C, BFU-E, CFU-E). Two animals were studied for extended periods of time: 8 and 24 months. Each has demonstrated a pattern wherein positive periods are interspersed with times when there were no detectable G418-resistant cells. We conclude that retroviral-mediated gene transfer can be used to insert genes into early progenitor cells of fetal sheep in utero and that the animals can continue to demonstrate blood cells expressing the gene for more than 2 years after birth. This is a US government work. There are no restrictions on its use. |
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