Gene electrotransfer: from biophysical mechanisms to in vivo applications : Part 1- Biophysical mechanisms

Abstract

Electropulsation is one of the nonviral methods successfully used to deliver genes into living cells in vitro and in vivo. This approach shows promise in the field of gene and cellular therapies. The present review focuses on the processes supporting gene electrotransfer in vitro. In the first part, we will report the events occurring before, during, and after pulse application in the specific field of plasmid DNA electrotransfer at the cell level. A critical discussion of the present theoretical considerations about membrane electropermeabilization and the transient structures involved in the plasmid uptake follows in a second part.

Keywords: Biophysical mechanisms; Electropermeabilization; Electroporation; Gene electrotransfer; Membranes.

Fig. 1

Differents models of gene electrotransfer. Model i: a The electric pulse induces a macrodefect (2r > 20 nm) and an electrophoretically mediated DNA accumulation. b After the pulse, a free diffusion of DNA takes place across the long-lived macropore. Model ii: a DNA is preadsorbed with the plasma membrane by an interaction with cationic lipids, sphingosines. b DNA is transiently inserted in plasma membrane. c DNA is electrophoretically pulled through the permeabilized zones. d DNA leaves the membrane and enters into the cell. Model iii: a The electric pulses induce the membrane permeabilization. b DNA is concentrated near the membrane surface and pushed through the putative electropores by electrophoretic forces. c The mechanical interaction between the pores and the DNA driven by electrophoretic forces induces an adjustment of pore sizes. c DNA enters into the cell. Model iv: a DNA remains at the interfacial region when no pore is present. b Under high electric field, the DNA diffuses towards the interior of the bilayer after a pore is created beneath it. c Diffusion of the strand toward the interior of the membrane leads to a complex DNA/lipid in which the lipid head groups encapsulate the DNA. d After the electric field pulse, the DNA is translocated. e DNA enters into the cell