Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin
(2008) Human Gene Therapy — Vol. 19, n° 11, p. 1261-1274 (2008)
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- Gene electrotransfer is gaining momentum as an efficient methodology for non-viral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of the DNA towards or across the permeabilized membrane. To investigate this further, combinations of permeabilizing short high voltage pulses (HV) and mainly electrophoretic long low voltage pulses (LV) were investigated in muscle, liver, tumor and skin in rodent models. (1) Striking differences between the different tissues were found, likely related to cell size and tissue organization. (2) Gene expression is increased, if there is 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 liver. (4) Efficient gene electrotransfer was achieved with HV field strengths below the detectability thresholds for permeabilization. (5) The lag time interval between the HV and LV decreased sensitivity to the HV pulses, enabling a wider HV amplitude range. In conclusion, HV+LV pulses represent an efficient and safe option for future clinical trials and we suggest recommendations for gene transfer to different types of tissues.
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Andre, F., Gehl, J., Sersa, G., Préat, V., Hojman, P., Eriksen, J., Golzio, M., Cemazar, M., Pavselj, N., Rols, M.-P., Miklavcic, D., Neumann, E., Teissie, J., & Mir, L. M. (2008). Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin. Human Gene Therapy, 19(11), 1261-1274. https://doi.org/10.1089/hgt.2008.060 (Original work published 2008)