title: Gene expression in an intact ex-vivo skin tissue model following percutaneous delivery of cationic liposome-plasmid DNA complexes.
abstract: The skin represents an attractive site for the localised gene therapy of dermatological pathologies and as a potential antigen bioreactor following transdermal delivery. Potential also exists for the gene therapy of skin as a cosmetic intervention. The most exploited non-viral gene delivery system involves the complexation of cationic liposomes with plasmid DNA (pDNA) to form lipid:pDNA vectors that protect the DNA from nuclease-mediated degradation and improve transgene-cell interactions. Despite numerous studies examining the potential for these vectors in delivering genes to a variety of keratinocyte models, investigations into the topical application of such complexes to intact skin tissue is limited. This ex-vivo study, conducted with intact skin tissue derived from hairless mice, provides quantitative confirmation that topical administration of cationic lipid:pDNA complexes can mediate uptake and expression of reporter pDNA (33-fold higher compared with control) in viable epidermal tissue. The ex-vivo study design provides for intact skin tissue that has not been subjected to depilatory procedures of potential detriment to stratum corneum barrier function, and can be utilised for the quantitative and efficient examination of a potentially wide range of non-viral gene vectors designed for epidermal expression.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Cardiff, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Birchall
authors.forename: C
authors.initials: C
authors.lastname: Marichal
authors.forename: L
authors.initials: L
authors.lastname: Campbell
authors.forename: A
authors.initials: A
authors.lastname: Alwan
authors.forename: J
authors.initials: J
authors.lastname: Hadgraft
authors.forename: M
authors.initials: M
authors.lastname: Gumbleton
mesh_terms: D000287:Administration, Topical; D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics*; D004337:Drug Carriers; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008854:Microscopy, Electron; D010957:Plasmids; D012867:Skin / Q000378:metabolism* / Q000648:ultrastructure; D012869:Skin Absorption
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D004247:DNA