Suicide gene therapy: a promising approach towards gene delivery

Abstract

Nowadays, among various gene therapy methods for cancer, the use of suicide gene therapy is gaining the interest of researchers because it has shown great potential for the treatment of cancer in an efficient manner than conventional cancer chemotherapies. In this therapy, a gene, encoding for an enzyme of non-mammalian origin which possess ability to change a nontoxic, safe prodrug into metabolites which are toxic to cells, is delivered to the cancer cells. As a result, the activated prodrug demonstrate killing effect on the transfected cancer cells as well as non-transfected cells by exhibiting bystander effect either via gap junctions or by several other mechanisms. Despite noteworthy advancements that has been made in the field of suicide gene therapy, this approach has not delivered significant outcomes in clinical trials and even a single enzyme/prodrug system has not made its way to clinic due to several challenges. The main issues that are hampering the applicability of suicide gene therapy from bench to bedside include slow prodrug to drug conversion rate, inadequate transfection/transduction efficiency of the vectors, and nonspecific toxicity/immunogenicity issues due to the delivery systems, plasmid DNA, enzymes, and prodrugs. This review provides a comparative synopsis of the various vectors involved in gene therapy along with an overview of the suicide gene therapy with special emphasis on most widely used enzyme/prodrug systems.