Retroviral Coexpression of Thymidylate Synthase and Dihydrofolate Reductase Confers Fluoropyrimidine and Antifolate Resistance (original) (raw)

1998, Biochemical and Biophysical Research Communications

myelosuppression has advanced to clinical trials (8-10). Retroviral gene transfer of dominant selectable Second, drug resistance genes can function as domimarkers into hematopoietic cells can be used to select nant selectable markers and allow for the selection and genetically modified cells in vivo or to attenuate the expansion of genetically modified cells (1,6). In light of toxic effects of chemotherapeutic agents. We show that results from clinical trials which routinely show low retroviral gene transfer of thymidylate synthase (TS) level transduction of cells capable of hematopoietic reconfers resistance to TS directed anticancer agents constitution, in vivo or ex vivo selection and expansion and that co-expression of TS and dihydrofolate reducof genetically modified cells may be necessary for the tase (DHFR) confers resistance to TS and DHFR cytosuccessful application of gene therapy for hematopoitoxic agents. Retroviral vectors encoding Escherichia etic disorders (11-14).

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