a tumour-specific promoter. A suitable promoter should be active in the tumour but inactive in the majority of normal tissue, particularly the liver, which is the organ that is most exposed to blood born viruses. Many such promoters have been identified and studied for the treatment of a range of cancers. Similarly, viral replication can be finely tuned with the use of microRNAs (miRNA) artificial target sites or miRNA response elements (MREs). Differential expression of miRNAs between healthy tissues and tumors permit to engineer oncolytic viruses detargeted from certain tissues of interest while allowing its replication in the tumor cells. Double targeting with both transductional and non-transductional targeting methods is more effective than any one form of targeting alone. Reporter genes Both in the laboratory and in the clinic it is useful to have a simple means of identifying cells infected by the experimental virus. This can be done by equipping the virus with "reporter genes" not normally present in viral genomes, which encode easily identifiable protein markers. One example of such proteins is GFP (green fluorescent protein) which, when present in infected cells, will cause a fluorescent green light to be emitted when stimulated by blue light. An advantage of this method is that it can be used on live cells and in patients with superficial infected lesions, it enables rapid non-invasive confirmation of viral infection. Another example of a visual marker useful in living cells is luciferase, an enzyme from the firefly which in the presence of luciferin, emits light detectable by specialized cameras. The E. coli enzymes beta-glucuronidase and beta-galactosidase can also be encoded by some viruses. These enzymes, in the presence of certain substrates, can produce intense colored compounds useful for visualizing infected cells and also for quantifying gene expression. Modifications to improve oncolytic activity Oncolytic viruses can be used against cancers in ways that are additional to lysis of infected cells. Suicide genes Viruses can be used as vectors for delivery of suicide genes, encoding enzymes that can metabolise a separately administered non-toxic pro-drug into a potent cytotoxin, which can diffuse to and kill neighbouring cells. One herpes simplex virus, encoding a thymidine kinase suicide gene, has progressed to phase III clinical trials. The herpes simplex virus thymidine kinase phosphorylates the pro-drug, ganciclovir, which is then incorporated into DNA, blocking DNA synthesis. The tumour selectivity of oncolytic viruses ensures that the suicide genes are only