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AssigneeCayla
InventorsGerard Tiraby, Jean-Paul Reynes, Michele Tiraby, Christophe Cazaux, Daniel Drocourt
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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.
A eukaryotic vector containing two expression suicide gene units, a first expression suicide gene unit which sensitizes tumor cells to 5-fluorocytosine and a second expression suicide gene unit which sensitizes mammalian cells or HIV-infected cells to Azidothymidine or other pyrimidine nucleoside analogs, wherein the first and second expression suicide gene units comprise a hybrid gene coding for a single protein having both cytosine deaminase and uracil phosphoribosyl transferase activities.
A eukaryotic vector containing an expression suicide gene unit comprising a hybrid gene coding for a single protein having both cytosine deaminase and uracil phosphoribosyl transferase activities.
A eukaryotic vector according to claim 18 wherein the two fungal genes are the fcy1 gene encoding cytosine deaminase and the fur1 gene encoding uracil phosphoribosyl transferase from Saccharomyces cerevisiae.
A eukaryotic vector containing an expression suicide gene unit which sensitizes mammalian cells or HIV-infected cells to Azidothymidine or other pyrimidine nucleoside analogs, wherein said expression suicide gene unit comprises a tmk gene from Escherichia coli encoding thymidylate kinase.
A hybrid gene coding for a single protein having both cytosine deaminase and uracil phosphoribosyl transferase activities.
A hybrid gene formed by the fusion of a tmk gene from Escherichia coli encoding thymidylate kinase and a tdk gene encoding thymidine kinase from Escherichia coli, said hybrid gene coding for a single protein with both thymidine kinase and thymidylate kinase activities.
A hybrid gene formed by the fusion of a tmk gene from Escherichia coli encoding thymidylate kinase and a ndk gene from Escherichia coli encoding nucleoside diphosphokinase, said hybrid gene coding for a single protein with both thymidylate kinase and thymidine diphosphokinase activities.
An expression suicide gene unit comprising a tk gene from human Varicella-Zoster virus encoding thymidine kinase and thymidylate kinase activities.
An expression suicide gene unit comprising a tk gene from human Epstein-Barr virus encoding thymidine kinase and thymidylate kinase activities.
Dependencies are inferred from the claim text.