Nucleic acid electrotransfer in mammalian cells: Mechanistic description

Abstract

The development of new drugs depends greatly on their successful, efficient, low cost, and safe delivery into target cells or tissues. In the case of highly charged macromolecules such as nucleic acids, the therapeutic effectiveness is mainly limited by their bio-distribution within the tissue and the poor permeability of the plasma membrane of cells. For this purpose, electroporation appears as a promising method for nucleic acid delivery. Electroporation is a physical method of vectorization that consists of application of electric pulses on cells or tissues. Optimization of the pulses' parameters leads to the transient permeabilization of the plasma membrane for molecules which otherwise cannot enter the cell. Therefore, the understanding of different principles of drug and gene delivery is necessary and needs to be taken into account according to the specificity of their delivery to tumors and/or normal tissues. This approach has been routinely used in cell biology for more than 30 years for cell transfection and in medicine in a number of clinics and hospitals through Europe to treat cutaneous cancers by increasing the toxicity of anticancer drugs (electrochemotherapy); it is also now under clinical trials for nucleic acid delivery (electrogenotherapy, electrovaccination). The present chapter focuses on electrotransfer of nucleic acids, the nature of nucleic acids (plasmid DNA, mRNA, siRNA, LNA, etc.) which can be electrotransferred, and the mechanism of their electrotransfer.