Electric Field‐Induced Cell Membrane Permeabilization and Gene Transfer: Theory and Experiments

The permeabilization and gene transfer phenomena in terms of the effect of electric field and cell parameters are reviewed in this paper. Electropermeabilization designates the use of short high‐voltage pulses to overcome the barrier of the cell membrane. A position‐dependent modulation of the membrane potential difference is induced, leading to a transient and reversible local membrane alteration. The electro‐induced permeabilization is long lived. A free exchange of hydrophilic molecules takes place across the membrane. The fraction of the cell surface which is competent for exchange is a function of the field intensity. The level of local exchange is strongly controlled by the pulse duration. This permeabilized state can be used to load cells with a variety of different molecules, either through simple diffusion in the case of small molecules, or through a multi‐step process as is the case for DNA transfer involving the electrophoretically driven association of the macromolecule with the destabilized membrane and its subsequent passage. Electropermeabilization is now in use for the delivery of a large variety of molecules: from ions to drugs, dyes, tracers, antibodies, oligonucleotides, RNA and DNA. While most studies are performed in vitro in cells in culture, an increasing number of data are obtained in vivo on tissues. However, membrane molecular and cell metabolic changes remain for the most part poorly understood. Therefore it is of great importance to elucidate the underlying phenomena both for the in vitro use of the method in terms of efficiency but also for the in vivo use of the method in terms of security.