11.2.2.1 Pro-drug Activation Vectors

One idea is to deliver a gene to a target cell whose product will activate a prodrug, which then kills the manipulated cell but does not affect the normal cells. Several experimental models are now in progress. These models use viral vector that carries a gene, its product would activate the non-toxic drug to be toxic only in the cancerous cell. For example the thymidine kinase gene, carried by a retrovirus, injected to the brain tumour to deliver the Thymidine kinase (Fig .17). The patient is then treated with the drug ganciclovir.  This drug is an analogue of guanosine.  It could be phosphorylated by thymidine kinase, which can be incorporated into DNA. Such incorporation inhibits DNA replication and kills the cell (Dachs, et al 1997).

Figure 17 : prodrug activation

Other example is a viral vector carries the gene for enzyme cytosine deaminase. This enzyme activates the non-toxic pro-drug 5-flurorcysteine to the toxic chemotherapeutic drug 5-fluorouracil, that kills the cancerous cells as a result of its interference with m-RNA metabolism (Licht , et al 1997) .