Gene expression in an intact ex-vivo skin tissue model following percutaneous delivery of cationic liposome-plasmid DNA complexes

The skin represents an attractive site for the localised gene therapy of de rmatological pathologies and as a potential antigen bioreactor following tr ansdermal delivery. Potential also exists for the gene therapy of skin as a cosmetic intervention. The most exploited non-viral gene delivery system i nvolves the complexation of cationic liposomes with plasmid DNA (pDNA) to f orm lipid:pDNA vectors that protect the DNA from nuclease-mediated degradat ion and improve transgene-cell interactions. Despite numerous studies exami ning the potential for these vectors in delivering genes to a variety of ke ratinocyte models, investigations into the topical application of such comp lexes to intact skin tissue is limited. This ex-vivo study, conducted with intact skin tissue derived from hairless mice, provides quantitative confir mation that topical administration of cationic lipid:pDNA complexes can med iate uptake and expression of reporter pDNA (33-fold higher compared with c ontrol) in viable epidermal tissue. The ex-vivo study design provides for i ntact skin tissue that has not been subjected to depilatory procedures of p otential 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. (C) 2000 Publ ished by Elsevier Science B.V. All rights reserved.