Genetic correction of inherited epidermal disorders

Genetic correction of monogenic human skin disorders represents a potential ly effective molecular therapy for severe diseases in which current therapy is only palliative. The stratified epithelium of the epidermis represents the tissue location with the largest number of genetic skin diseases yet ch aracterized. Specific requirements of successful gene delivery in this sett ing include correct targeting within tissue, durability, and a lack of immu nogenecity. Progress toward this goal has advanced from identification of d isease genes to reintroduction of wild-type genes to patient cell lines and primary cells in vitro. This initial work has been extended to gene-based correction of diseased tissue regenerated in vivo in the form of human pati ent skin xenografts on immune-deficient mice. Efforts in this human tissue model have laid the foundation for future efforts to extend this progress t oward ex vivo cutaneous gene therapy trials in humans.