Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

The secretion of polypeptides by prokaryotic and eukaryotic cells is an elaborate mechanism enabling the execution of essential processes like active modulation of the environment, enzymatic processing of nutrients and communication with other cells. However, a unique group of secreted polypeptides, the secreted toxins, plays a different role in maintaining the fitness of the organism, and have been perfected through evolution with the aim of damaging other living organisms. As such, toxins provide their producer with advantages such as enhanced defense capabilities or pathogenic OPEN ACCESS competence. Most natural protein toxins can be divided into three major groups: 1. Toxins that damage the cell by disrupting membrane integrity; 2. Toxins that disrupt the normal electrical activity of the nervous system of the intoxicated organism; 3. Toxins that disrupt or interfere with cellular processes by virtue of an enzymatic activity. Members of groups 1 and 2 may affect the target cells by enzymatic or non-enzymatic activities. Some members of the third group, on which this review is focused, are extremely toxic polypeptides that have the capability of self translocation into the cell cytoplasm where they execute their activity that, in most cases, leads to death of the intoxicated cell. Scientific advances in the last decades facilitated the processing and manipulation of biological substances; among which are toxic polypeptides and their encoding genes. By using different strategies for directing toxic moieties to diseased cells/tissues (Figure 1) , scientists have established a new niche in clinical research, called "toxin-based therapy".