Advances in skin gene therapy

Specific anatomical and biological properties make the skin a very interest ing target organ for gene therapy approaches. Different cell types of the e pidermis, such as keratinocytes, melanocytes, or dendritic cells, can be ge netically modified to treat a broad spectrum of diseases, including genetic ally inherited skin disorders, tumour diseases, metabolic disorders and inf ectious diseases. The easy accessibility of skin suggests that different me thods for gene delivery can be pursued, depending on the desired applicatio n. The approach used to deliver DNA to the skin will influence not only the efficiency of DNA delivery, but also the level and duration of transgene e xpression. Furthermore, the desired biological effect will also influence t he decision of which gene transfer method is the best choice. Among the cur rent challenges of cutaneous gene therapy are: optimising the efficiency of direct in vivo gene delivery; targeting specific epidermal cells, includin g keratinocyte stem cells; achieving sustained gene expression and regulati ng gene expression in vivo. This review summarises recent advances in the f ield of skin gene therapy and evaluates possible strategies to overcome obs tacles and achieve successful clinical applications of skin gene therapy.