Cutaneous gene expression of plasmid DNA in excised human skin following delivery via microchannels created by radio frequency ablation.
The skin is a valuable organ for the development and exploitation of gene medicines. Delivering genes to skin is restricted however by the physico-chemical properties of DNA and the stratum corneum (SC) barrier. In this study, we demonstrate the utility of an innovative technology that creates transient microconduits in human skin, allowing DNA delivery and resultant gene expression within the epidermis and dermis layers. The radio frequency (RF)-generated microchannels were of sufficient morphology and depth to permit the epidermal delivery of 100 nm diameter nanoparticles. Model fluorescent nanoparticles were used to confirm the capacity of the channels for augmenting diffusion of macromolecules through the SC. An ex vivo human organ culture model was used to establish the gene expression efficiency of a beta-galactosidase reporter plasmid DNA applied to ViaDerm treated skin. Skin treated with ViaDerm using 50 microm electrode arrays promoted intense levels of gene expression in the viable epidermis. The intensity and extent of gene expression was superior when ViaDerm was used following a prior surface application of the DNA formulation. In conclusion, the RF-microchannel generator (ViaDerm) creates microchannels amenable for delivery of nanoparticles and gene therapy vectors to the viable region of skin.
Gene Delivery Research Group, Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3XF, and Gwent Healthcare NHS Trust, Royal Gwent Hospital, South Wales, UK. birchalljc@cardiff.ac.uk
James
J
Birchall
Sion
S
Coulman
Alexander
A
Anstey
Chris
C
Gateley
Helen
H
Sweetland
Amikam
A
Gershonowitz
Lewis
L
Neville
Galit
G
Levin
D000279:Administration, Cutaneous; D000368:Aged; D017115:Catheter Ablation; D004247:DNA / Q000008:administration & dosage*; D004560:Electricity; D004566:Electrodes; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D049329:Nanostructures; D010957:Plasmids; D012867:Skin / Q000378:metabolism*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D004247:DNA; D001616:beta-Galactosidase