Liposome-medicated gene transfer and expression via the skin.
A beta-galactosidase gene expression construct was used to investigate the effectiveness of gene delivery and expression when DNA/liposome complexes were topically applied to mouse skin in vivo. DNA was complexed with commercial preparation of N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl-ammonium-methyl-sulp hate (DOTAP) in a ratio of 1:1.6 (w/w). The DNA rapidly penetrated the skin and was expressed in the epidermis, dermis and hair follicles. A DNA concentration of 267 microgram/ml DNA was found to be optimal for efficient transfection. Expression was seen as early as 6 h post-application, persisted at high levels 24 and 48 h post-treatment, but was markedly reduced by 7 days after application. In conclusion, utilising a commercially available liposome preparation, topically-applied DNA/liposome complexes can be efficiently delivered and expressed in several cell types within the skin. This simple, non-invasive technique may have implications for a number of gene therapy applications.
Alexander
M Y
MY
Department of Medical Genetics, Glasgow University, Yorkhill Hospital, UK.
Akhurst
R J
RJ
D000279:Administration, Cutaneous; D000818:Animals; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D008081:Liposomes / Q000378:metabolism*; D008297:Male; D051379:Mice; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D008081:Liposomes; D004247:DNA; D001616:beta-Galactosidase