Gene delivery to the skin - how far have we come?

Gene therapies are powerful tools to prevent, treat, and cure human diseases. The application of gene therapies for skin diseases received little attention so far, despite the easy accessibility of skin and the urgent medical need. A major obstacle is the unique barrier properties of human skin, which significantly limits the absorption of biomacromolecules, and thus hampers the efficient delivery of nucleic acid payloads. In this review, we discuss current approaches, successes, and failures of cutaneous gene therapy and provide guidance toward the development of next-generation concepts. We specifically allude to the delivery strategies as the major obstacle that prevents the full potential of gene therapies - not only for skin disorders but also for almost any other human disease