Suicide genes and combinations of pyrimidine nucleoside and nucleobase analogues with suicide genes for gene therapy

摘要

The present invention relates to two groups of suicide hybrid genes in which genes from one group specifically activate the pyrimidine nucleobase analog 5-fluorocytosine and genes from the other group activate the pyrimidine nucleoside analog azidothymidine to derivatives toxic for mammalian cells.The present invention further relates to methods for the selective killing of transfected tumor cells or immune cells using a single suicide hybrid gene or the combination of two suicide hybrid genes selected for a complementarity in their antimetabolic action. The present invention also relates to eukaryotic vectors comprising two expression suicide gene units, the first permitting the sensitization of tumor cells to 5-fluorocytosine and the second permitting the sensitization of HIV-infected cells to Azidothymidine in a synergistic fashion.