Abstract: Compositions for targeting expression of a gene such as an antitumor gene may contain a first nucleic acid construct in which expression of a first gene is controlled by a first promoter whose function is suppressed in non-tumor cells, and a second nucleic acid construct in which expression of a second gene for down-regulating the first gene in non-tumor cells is controlled by a second promoter that is up-regulated in non-tumor cells. The second promoter may be regulated by means of p53 binding, targeting expression of the first gene to cells in which p53 down-regulation of expression is disrupted, e.g. cells in which p53 is mutated. The first promoter may be one which is unregulated in tumor cells, for example the Hsp70 promoter which is upregulated in mutant p53 tumor cells. A suitable antitumor agent in thymidine kinase.