Transdermal gene delivery holds significant advantages as it is able to minimize the problems of systemic administration such as enzymatic degradation, systemic toxicity, and poor delivery to target tissues. This technology has the potential to transform the treatment and prevention of a range of diseases. However, the skin poses a great barrier for gene delivery because of the “bricks-and-mortar” structure of the stratum corneum and the tight junctions between keratinocytes in the epidermis. This review systematically summarizes the typical physical and chemical approaches to overcome these barriers and facilitate gene delivery via skin for applications in vaccination, wound healing, skin cancers and skin diseases. Next, the advantages and disadvantages of different approaches are discussed and the insights for future development are provided.

透皮基因传递具有显着的优势，因为它能够最大程度地减少全身性给药的问题，例如酶促降解，全身毒性以及对靶组织的不良传递。该技术具有改变多种疾病的治疗和预防的潜力。然而，由于角质层的“砖和灰浆”结构以及表皮中角质形成细胞之间的紧密连接，皮肤对基因传递构成了很大的障碍。这篇综述系统地总结了典型的物理和化学方法，以克服这些障碍并促进基因通过皮肤的传递，以用于疫苗接种，伤口愈合，皮肤癌和皮肤疾病。接下来，讨论了不同方法的优缺点，并提供了对未来发展的见解。