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| Title: | Double mutants of dihydrofolate reductase and methods of using same |
| Inventors: | Bertino, Joseph R.; New York, NY, USA Ercikan-Abali, Emine A.; New York, NY, USA Banerjee, Debabrata; New York, NY, USA Mineishi, Shin; New York, NY, USA Sadelain, Michel; New York, NY, USA |
| Summary: | Described herein are human dihydrofolate reductase double mutants, and methods and uses thereof. The double mutants are described as having substitutions at positions 22 and 31, and with properties superior to the previously disclosed mutants. Specific mutant forms include Ser31Tyr22, Ser31Phe22, Gly31Tyr22, Gly31Phe22, Ala31Tyr22 and Ala31Phe22. Methods are described by which the mutant DHFR may be used as a selectable marker, and in the modification of the genome of human cells, particularly bone marrow cells or peripheral blood stem cells. Therapeutic applications are included, such as in protecting bone marrow or blood stem cells from chemotherapy using antifolate agents. |
| Abstract: | 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. |
| US Patent Website: | Click Here for Full Text of Patent |
| Title Number: | US6887467 |
| Application Number: | US2003000650417 |
| Date Filed: | 27/08/2003 |
| Date Published: | 03/05/2005 |
| Assignee: | Sloan-Kettering Institute for Cancer Research, New York, NY, USA |