Takis Scientists are among the pioneers of in vivo electro-gene-transfer of plasmid DNA (DNA-EGT). This has been shown to be a safe methodology resulting in greater DNA cell uptake, enhanced protein expression and concomitant increase in longer term immune responses against the target antigen in a variety of species. DNA-EGT can be administered repeatedly to boost immune responses as required for the maintenance of anti-tumor immunity. The approach uses brief electrical pulses that create transient "pores" in the cell membranes, which allowing large molecules such as DNA or RNA to enter the cell cytoplasm. In addition, the electrical gradient inside the tissue allows transportation of the transduced DNA molecule inside cell nuclei. Immediately following cessation of the electrical field, the pores seal without causing cell death. Typically, milli- and microsecond pulses have been used for EGT. In addition to the increased gene expression, EGT is believed to enhance immune responses through increased secretion of inflammatory chemokines and cytokines, and recruitment of APCs at the EGT site and trafficking to the draining lymph nodes. As a result, both antigen-specific humoral and cellular immune responses from EGT mediated delivery of plasmid DNA are higher than levels achieved by intramuscular injection of DNA alone.
Takis is collaborating with IGEA to further optimize this technology and plans to use Cliniporator in future clinical trials