Transdermal transport of DNA antisense oligonucleotides by electroporation.
Fluorescein-labeled antisense oligodeoxynucleotides (ODNs) corresponding to the promoters of the protooncogene c-myb (24-mer) and the oncogene c-myc (15-mer) were transported through the human skin in vitro by electroporation. Fluxes of 6.4 +/- 2.1 pM/cm2* hr and 11.5 +/- 3.5 pM/cm2* hr, respectively, were achieved during exponential pulsing [tau pulse = 1.1ms, transdermal voltage (Uskin) = 80V] every five seconds. The flux for Uskin < 70V was undetectable, rapidly increased at 80V, but plateaued at higher values. Fluorescence imaging demonstrated that transport of the ODNs is concentrated in localized transport regions (LTRs)1 approximately 30 microns in diameter.
Zewert
T E
TE
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Pliquett
U F
UF
Langer
R
R
Weaver
J C
JC
D001483:Base Sequence; D001692:Biological Transport; D018274:Electroporation; D019793:Fluorescein; D005452:Fluoresceins; D016259:Genes, myc; D006801:Humans; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D012867:Skin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D005452:Fluoresceins; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D019793:Fluorescein