The development of anticancer drug-controlled gene expression system

Gene therapy for induction of immune response has been a cutting-edge technology for quite some years. Nevertheless, a major drawback of such technology was the control of foreign gene expression. In the case of an overexpression of immune system controlling genes may result in the induction of autoimmune diseases. This way the implementation damage of gene therapy for immune response activation does not meet the obtained benefits. Nevertheless, a specific stimulation of immune system has an immense potential in the field of cancer therapy, since an active and fully functional immune system can recognize and destroy the tumors within a body of the patient without a use of the conventional treatment. Here we present an in vitro study that does show the feasibility of time-controlled gene expression when gene delivery to the cells is performed simultaneously with cytotoxic drug bleomycin. The method of electroporation was used for the delivery of gene and anticancer drug to the cells. The selection of electroporation as a vector of gene and drug delivery to the cell was based on the application properties that are already in use, namely clinical anticancer drug delivery to the tumors (electrochemotherapy) and electroporation gene therapy. Previously, it has been shown that intracellular transfer of anticancer drug bleomycin via electroporation result in cells death only in between 24 - 72 hours [1]. Routinely, transfection efficiency after successful electrotransfer is measured after 24 hours. Therefore, it was decided to combine both methods in order to obtain temporal control of transfection efficiency. Results clearly indicate a successful cellular transfer of both molecules: bleomycin (anticancer drug), and plasmid DNA (pmax-GFP), thus obtaining a high transfection efficiency within 72 hours and death of the same transfected cells after 72 hours. Moreover, unexpectedly, a combined technique also induced a higher efficiency of anticancer drugs. [...]Biologijos katedraGamtos mokslų fakultetasVytauto Didžiojo universiteta