Assessing the efficiency of In Vivo electroporation as a nonviral gene transfer technique and studying its application in antiangiogenic cancer gene therapy and cancer immunotherapy

Electroporation refers to a technique that makes use of electrical pulses to create transient and reversible pores into cellular membranes which allows the passage of drugs and macromolecules, such as plasmid DNA, into the cell's interior. It is a widely used laboratory procedure for the transfection of cultured mammalian cells, plant cells and bacteria. Only recently has in vivo electroporation been used for the transfer of genetic material into living tissue, such as muscle, hepatocytes, and tumors of experimental animals. Using a luciferase assay, we have shown that electroporation-mediated luciferase gene transfer into solid, subcutaneous tumors in mice resulted in a 103 fold increase in tumor luciferase activity compared to naked DNA injections. Using this technique, we succeeded in inhibiting the growth of LLC tumors in mice by delivering plasmid DNA encoding mouse Endostatin and mouse single-chain IL-12 directly into the tumor site. Lastly, in vivo electroporation was used to enhance DNA vaccination with the tumor associated antigen CEA and IL-12 gene adjuvant, which protected mice from a tumor challenge with LLC/CEA+ tumor cells. Our results suggest that in vivo electroporation is an efficient nonviral, gene transfer vehicle that can be used in the fields of antiangiogenic cancer gene therapy as well as cancer immunotherapy