Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

The delivery of genetic material into target cells for the purpose of gaining a therapeutic effect is generally known as "gene therapy" (for review, see [313] [314] [315] [316] [317] [318] [319] [320] [321] [322] [323] ). Advances in molecular biology, virology and nanotechnology in the past decade enabled the development of a variety of viral and non-viral gene delivery systems [324] [325] [326] . When the death of the target cell is the desired therapeutic outcome of the transgene delivery, the process is termed "suicide gene therapy" and involves delivery of genes whose products are either toxic, proapoptotic or have the ability to activate precursors of toxic drugs ("pordrugs") [327] [328] [329] [330] [331] . In order to minimize damage to healthy tissue, a specific targeting mechanism must be applied and transcriptional targeting is a very common strategy. The method is based on positioning the suicide gene to be transferred under the transcriptional regulation of a promoter/element which is specifically or at least preferentially active in the target tissue [332] [333] [334] [335] [336] [337] [338] . If transcription of a toxin encoding gene is controlled by such a target specific promoter, eradication of undesirable cell population is feasible with minimal collateral damage ( Figure 1 ). The next chapter reviews some of the prominent toxin-based suicide gene therapy studies and developments which are classified by their target disease; the majority of them were evaluated at a preclinical level and aimed at cancer therapy. Information about suicide gene constructs developed in these and other studies are summarized in Table 2 . * Refers to the name of the gene/gene product whose transcriptional regulatory elements were used to drive the expression of a toxic gene in target cells.