In Vivo Selection of Primitive Hematopoietic Cells (SJ-95-0010)

Technology Name
(St. Jude Reference #)
In Vivo Selection of Primitive Hematopoietic Cells
Description This invention describes a method that selects genetically modified hematopoietic progenitor or stem cells from unmodified hematopoietic cells. This is achieved by introducing a mutant dihydrofolate reductase (DHFR) gene that confers antifolate resistance into hematopoietic progenitor or stem cells and then administering an antifolate, which inhibits the growth of unmodified cells and a nucleoside transport inhibitor to block the salvage pathway. Cells that do not have the mutant DHFR gene cannot synthesize new nucleosides and the salvage for exogenous nucleosides is also blocked; therefore growth of unmodified cells is arrested. The invention also includes nucleic acids which encode mutant DHFR genes and hematopoietic cells transformed with such mutant genes.
Keywords  Gene therapy, DHFR
Granted Patents or Published Applications US Patent No. 6,500,421
Related Scientific References Allay, JA., et al., "In vivo Selection of Retrovirally Transduced Hematopoietic Stem Cells" Nature Medicine 4: 1136-1143 (1998)
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Last update: June 2006