Patent ID: 6500421
Filing Date: 2002-12-31
Classification: A61K

Abstract:
A method of in vivo selection for genetically modified hematopoietic progenitor cells from nonmodified hematopoietic cells in a subject comprising:a. genetically modifying hematopoietic progenitor cells by introducing into the cells a nucleic acid comprising a sequence encoding a mutant dihydrofolate reductase which when expressed can confer antifolate resistance; b. administering to the subject the genetically modified hematopoietic progenitor cells; c. administering to the subject an antifolate in an amount which inhibits the growth of the nonmodified hematopoietic cells, wherein the inhibition of the nonmodified hematopoietic cells by the antifolate can be offset in vivo by nucleoside salvage; and d. administering to the subject a suitable nucleoside transport inhibitor in an amount effective to prevent the offset of the inhibitory effect of the antifolate in the nonmodified hematopoietic cells, whereby the combination of the antifolate and the nucleoside transport inhibitor selects in vivo for the genetically modified hematopoietic progenitor cells.