| abstract |
(57) [Summary] A composition targeting the expression of a gene such as a non-tumor gene comprises a first promoter (2,2) whose function is to suppress the expression of the first gene (1) in non-tumor cells. A first nucleic acid construct controlled by 3), and a second promoter in which expression of a second gene (4) is up-regulated in non-tumor cells to down-regulate the first gene in non-tumor cells A second nucleic acid construct controlled by (5,6). The second promoter is regulated by p53 binding and can target expression of the first gene to cells in which p53 downstream regulation of expression has been disrupted, such as cells in which p53 is mutated. The first promoter is one that is up-regulated in tumor cells, such as the Hsp70 promoter that is up-regulated in mutant p53 tumor cells. A suitable non-tumor reagent is thymidine kinase, which has been shown to use the composition to provide a specific cell killing function for tumor cells as opposed to non-tumor cells. |