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E DelaFlor-Weiss, C Richardson, M Ward, A Himelstein, L Smith, S Podda, M Gottesman, I Pastan and A Bank
Department of Genetics and Development, Columbia University College of
Physicians and Surgeons, New York, NY 10032.
Gene therapy in humans requires the transplantation of genetically modified
cells, and it is important to select only those cells capable of expressing
high levels of protein from the transferred gene. Expression of the human
multiple drug resistance (MDR) gene confers resistance to a variety of
compounds in vitro and in vivo. To determine the feasibility of conferring
recipient erythroid cells with the MDR phenotype, we have transduced mouse
erythroleukemia cells (MELC) with the MDR gene in a retroviral vector. We
show here that MELC clones resistant to exposure to colchicine (an
MDR-responsive agent) can be isolated, and demonstrate high levels of MDR
RNA and protein expression. Increasing doses of colchicine increase the
level of MDR RNA and protein expression significantly. These results
indicate that it is possible to transfer and express the human MDR
phenotype in mouse erythroid cells by retrovirally mediated gene transfer,
and that drug selection can be used to enrich or purify populations of
cells containing and expressing this gene.
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||