Review

Molecular Biotechnology

, Volume 41, Issue 3, pp 286-295

First online:

What is (Still not) Known of the Mechanism by Which Electroporation Mediates Gene Transfer and Expression in Cells and Tissues

  • Jean-Michel EscoffreAffiliated withCNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale)Université de Toulouse, UPS, IPBS
  • , Thomas PortetAffiliated withCNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale)Université de Toulouse, UPS, IPBSLaboratoire de Physique Théorique - CNRS UMR 5152, IRSAMC, Université Paul Sabatier
  • , Luc WasunguAffiliated withCNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale)Université de Toulouse, UPS, IPBS
  • , Justin TeissiéAffiliated withCNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale)Université de Toulouse, UPS, IPBS
  • , David DeanAffiliated withLaboratoire de Physique Théorique - CNRS UMR 5152, IRSAMC, Université Paul Sabatier
  • , Marie-Pierre RolsAffiliated withCNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale)Université de Toulouse, UPS, IPBS Email author 

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Abstract

Cell membranes can be transiently permeabilized under application of electric pulses. This treatment allows hydrophilic therapeutic molecules, such as anticancer drugs and DNA, to enter into cells and tissues. This process, called electropermeabilization or electroporation, has been rapidly developed over the last decade to deliver genes to tissues and organs, but there is a general agreement that very little is known about what is really occurring during membrane electropermeabilization. It is well accepted that the entry of small molecules, such as anticancer drugs, occurs mostly through simple diffusion after the pulse while the entry of macromolecules, such as DNA, occurs through a multistep mechanism involving the electrophoretically driven interaction of the DNA molecule with the destabilized membrane during the pulse and then its passage across the membrane. Therefore, successful DNA electrotransfer into cells depends not only on cell permeabilization but also on the way plasmid DNA interacts with the plasma membrane and, once into the cytoplasm, migrates towards the nucleus. The focus of this review is to describe the different aspects of what is known of the mechanism of membrane permeabilization and associated gene transfer and, by doing so, what are the actual limits of the DNA delivery into cells.

Keywords

Gene transfer Gene expression Membrane Electric field Electroporation Electropermeabilization