Regulated cutaneous gene delivery: the skin as a bioreactor

Epidermal keratinocytes can secrete polypeptides into the bloodstream, and they can be easily expanded in culture and genetically modified. It is thus possible to use epidermal keratinocytes for the systemic delivery of transgene products. Here we review the development of epidermal secretory systems, from cultured keratinocytes to skin grafts and transgenic mouse models. We also discuss a gene-switch approach for regulated cutaneous gene delivery.