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.

基因疗法是预防、治疗和治愈人类疾病的有力工具。尽管皮肤容易获得且医疗需求迫切，但迄今为止，基因疗法在皮肤病中的应用很少受到关注。一个主要障碍是人体皮肤独特的屏障特性，它显着限制了生物大分子的吸收，从而阻碍了核酸有效载荷的有效传递。在这篇综述中，我们讨论了皮肤基因治疗的当前方法、成功和失败，并为下一代概念的发展提供了指导。我们特别提到传递策略是阻止基因疗法充分发挥潜力的主要障碍——不仅针对皮肤病，而且几乎针对任何其他人类疾病。