A MODEL FOR KERATINOCYTE GENE-THERAPY - PRECLINICAL AND THERAPEUTIC CONSIDERATIONS

Gene transfer to the skin is essential for correcting genetic disorder s and studying skin biology. Previous attempts at in vivo gene transfe r have employed replication-deficient adenovirus injected subcutaneous ly and plasmid DNA propelled by a gene gun. In this report, we used mo use skin as a model and evaluated the efficiency of these two methods. Using the luciferase reporter gene, we found that adenovirus injected subcutaneously transduced primarily cells in the dermis. However, par ticle bombardment of skill by gene gun delivered the reporter gene mai nly into the epidermis. When mouse skin was bombarded with a DNA const ruct expressing human TGF-alpha, the epidermis of the treated mice sho wed localized epidermal acanthosis and hypergranulosis, which resemble d the histological phenotype of previously described transgenic mice o verexpressing TGF-alpha in the epidermis. These results suggest that t he gene gun may be an effective tool for epidermal gene transfer and c ould be potentially useful in determining in vivo effects of growth fa ctors and cytokines on the epidermis.