1. Hum Gene Ther. 2008 Nov;19(11):1261-71.

Efficiency of high- and low-voltage pulse combinations for gene electrotransfer
in muscle, liver, tumor, and skin.

André FM, Gehl J, Sersa G, Préat V, Hojman P, Eriksen J, Golzio M, Cemazar M,
Pavselj N, Rols MP, Miklavcic D, Neumann E, Teissié J, Mir LM.

CNRS, UMR 8121, Institute Gustave-Roussy, F-94805 Villejuif Cédex, France.

Gene electrotransfer is gaining momentum as an efficient methodology for nonviral
gene transfer. In skeletal muscle, data suggest that electric pulses play two
roles: structurally permeabilizing the muscle fibers and electrophoretically
supporting the migration of DNA toward or across the permeabilized membrane. To
investigate this further, combinations of permeabilizing short high-voltage
pulses (HV; hundreds of V/cm) and mainly electrophoretic long low-voltage pulses 
(LV; tens of V/cm) were investigated in muscle, liver, tumor, and skin in rodent 
models. The following observations were made: (1) Striking differences between
the various tissues were found, likely related to cell size and tissue
organization; (2) gene expression is increased, if there was a time interval
between the HV pulse and the LV pulse; (3) the HV pulse was required for high
electrotransfer to muscle, tumor, and skin, but not to liver; and (4) efficient
gene electrotransfer was achieved with HV field strengths below the detectability
thresholds for permeabilization; and (5) the lag time interval between the HV and
LV pulses decreased sensitivity to the HV pulses, enabling a wider HV amplitude
range. In conclusion, HV plus LV pulses represent an efficient and safe option
for future clinical trials and we suggest recommendations for gene transfer to
various types of tissues.

PMID: 19866490 [PubMed - in process]