As the field of anticancer gene therapy edges closer to the mainstream, so we learn more of its current limitations as well as the potential for future success. With the technologies available today, it is simply not possible to achieve correction of every single genetic abnormality in every malignant cell. Hence most approaches investigated so far have involved a cytotoxic strategy, aiming to selectively destroy tumours while avoiding “collateral damage” to normal tissues.1

The success or failure of such cytotoxic gene therapy is influenced by two important choices—what therapeutic gene should be introduced and what vector should carry it to the target? We already have a range of genetic prodrug activation therapy (GPAT) strategies available, based on introducing tumour specific “suicide” enzymes that can generate toxic metabolites from otherwise benign prodrugs. Common examples include the herpes simplex virus thymidine kinase (HSVtk), which confers sensitivity to the antiviral drug ganciclovir, or theEscherichia coli derived cytosine deaminase that converts 5-fluorocytosine into the …