Electric pulse-mediated gene delivery to various animal tissues.
Electroporation designates the use of electric pulses to transiently permeabilize the cell membrane. It has been shown that DNA can be transferred to cells through a combined effect of electric pulses causing (1) permeabilization of the cell membrane and (2) an electrophoretic effect on DNA, leading the polyanionic molecule to move toward or across the destabilized membrane. This process is now referred to as DNA electrotransfer or electro gene transfer (EGT). Several studies have shown that EGT can be highly efficient, with low variability both in vitro and in vivo. Furthermore, the area transfected is restricted by the placement of the electrodes, and is thus highly controllable. This has led to an increasing use of the technology to transfer reporter or therapeutic genes to various tissues, as evidenced from the large amount of data accumulated on this new approach for non-viral gene therapy, termed electrogenetherapy (EGT as well). By transfecting cells with a long lifetime, such as muscle fibers, a very long-term expression of genes can be obtained. A great variety of tissues have been transfected successfully, from muscle as the most extensively used, to both soft (e.g., spleen) and hard tissue (e.g., cartilage). It has been shown that therapeutic levels of systemically circulating proteins can be obtained, opening possibilities for using EGT therapeutically. This chapter describes the various aspects of in vivo gene delivery by means of electric pulses, from important issues in methodology to updated results concerning the electrotransfer of reporter and therapeutic genes to different tissues.
Mir
Lluis M
LM
Laboratory of Vectorology and Gene Transfer, UMR 8121 CNRS Institut Gustave-Roussy, F-94805 Villejuif Cédex, France.
Moller
Pernille H
PH
André
Franck
F
Gehl
Julie
J
D000818:Animals; D001808:Blood Vessels / Q000293:injuries; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D004566:Electrodes; D018274:Electroporation / Q000295:instrumentation / Q000379:methods*; D018014:Gene Transfer Techniques / Q000009:adverse effects; D017930:Genes, Reporter; D015316:Genetic Therapy; D018482:Muscle, Skeletal / Q000378:metabolism; D012449:Safety; D014161:Transduction, Genetic
D004274:DNA, Recombinant