Thermal Assisted In Vivo Gene Electrotransfer

Abstract

Gene electrotransfer is an effective approach for delivering plasmid DNA to a variety of tissues. Delivery of molecules with electric pulses requires control of the electrical parameters to achieve effective delivery. Since discomfort or tissue damage may occur with high applied voltage, the reduction of the applied voltage while achieving the desired expression may be an important improvement. One possible approach is to combine electrotransfer with exogenously applied heat. Previous work performed in vitro demonstrated that increasing temperature before pulsing can enhance gene expres sion and made it possible to reduce electric fields while maintaining expression levels. In the study reported here, this combination was evaluated in vivo using a novel electrode device designed with an inserted laser for application of heat. The results obtained in this study demonstrated that increased temperature during electrotransfer increased expression or maintained expression with a reduction in applied voltage. With further optimization this approach may provide the basis for both a novel method and a novel instrument that may greatly enhance translation of gene electrotransfer.

Electrotransfer of siRNA to Silence Enhanced Green Fluorescent Protein in Tumor Mediated by a High Intensity Pulsed Electromagnetic Field

“…It was shown that gene electrotransfer could be thermally assisted. Specifically, heating applied prior to electroporation enabled a similar level of transfection efficiency in the skin using an approximately 30% lower electric field [62]. In our study, we observed an increase in the temperature of the magnetic coil (approximately 40 • C, data not shown), which could contribute to the transfection efficiency.…”

Safe and efficient novel approach for non-invasive gene electrotransfer to skin

“…Potential thermal damages might be induced by the electrical treatment 50 , 51 . A positive contribution was shown to be brought by a controlled heating of the skin where the electrotransfer was delivered 52 , 53 . The local heating of the skin was investigated as a potential parameter in the control of the gene expression.…”

Calcium electroporation and electrochemotherapy for cancer treatment: Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy

“…The effect of temperature on electropermeabilization has previously been described by Kanduser et al . 49 and an increase in temperature has recently been shown to increase gene expression following gene electrotransfer in addition to permit a decrease in the electrical field applied in gene electrotransfer in vivo 50 . The observed differences in effect of electroporation-based treatments might be more pronounced with higher temperature differences between samples.…”