TRANSDERMAL TRANSPORT OF DNA ANTISENSE OLIGONUCLEOTIDES BY ELECTROPORATION

Fluorescein-labeled antisense oligodeoxynucleotides (ODNs) correspondi ng to the promoters of the protooncogene c-myb (24-mer) and the oncoge ne c-myc (15-mer) were transported through the human skin in vitro by electroporation. Fluxes of 6.4+/-2.1 pM/cm(2) hr and 11.5+/-3.5 pM/cm (2) hr, respectively, were achieved during exponential pulsing [tau(p ulse) = 1.1ms, transdermal voltage (U-skin)= 80V] every five seconds. The flux for U-skin <70V was undetectable, rapidly increased at 80V, b ut plateaued at higher values. Fluorescence imaging demonstrated that transport of the ODNs is concentrated in localized transport regions ( LTRs)(1) approximately 30 mu m in diameter. (C) 1995 Academic Press, I nc.