New mutant forms of human dihydrofolate reductase (DHFR) which have properties
superior to the previously disclosed mutants have mutations at both amino acid
22 and amino acid 31. Specific mutant forms are Ser31Tyr22, Ser31Phe22,
Gly31Tyr22, Gly31Phe22, Ala31Tyr22 and Ala31Phe22. The mutant DHFR of the invention
may be used as a selectable marker, and to modify the genome of human cells, particularly
bone marrow cells or peripheral blood stem cells, to render them resistant to chemotherapy
using antifolate agents.
