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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: | This invention introduces a mutant form of human dihydrofolate reductase (DHFR), with substitutions at positions 22 and 31. Further disclosed are specific mutant forms such as Ser31Tyr22, Ser31Phe22, Gly31Tyr22, Gly31Phe22, Ala31Tyr22 and Ala31Phe22. Applications include use of the mutant DHFR as a selectable marker, and in the genomic modification of human cells, particularly bone marrow cells or peripheral blood stem cells, and in rendering such cells resistant to the toxic chemotherapeutic effects of 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 maybe 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: | US6642043 |
| Application Number: | US1999000142530 |
| Date Filed: | 20/01/1999 |
| Date Published: | 04/11/2003 |
| Assignee: | Sloan-Kettering Institute for Cancer Research, New York, NY, USA |