Kikuchi Yasushi, Tamai Katsuto, Kaneda Yasufumi
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
J Dermatol Sci. 2008 May;50(2):87-98. doi: 10.1016/j.jdermsci.2007.07.006. Epub 2007 Aug 31.
Over the past decade, many approaches to transferring genes into the skin have been investigated. However, most such approaches have been specifically aimed against genodermatosis, and have not produced sufficient results. The goal of such research is to develop a method in which genes are transferred easily, efficiently and stably into keratinocytes, especially into keratinocyte stem cells, and in which the transgene expression persists without a reaction from the host immune response. Although accidental development of cancer has occurred in trials of gene therapy for X-linked severe combined immunodeficiency (X-SCID), resulting in slowing of the progress of this research, the lessons of these setbacks have been applied to further research. Moreover, combined with the techniques acquired from tissue engineering, recent developments in our knowledge about stem cells will lead to new treatments for genodermatoses. The present review summarizes the methods by which therapeutic genes can be transferred into keratinocytes, with discussion of how gene transfer efficiency can be improved, with particular emphasis on disruption of the skin barrier function. It concludes with discussion of the challenges and prospects of keratinocyte gene therapy, in terms of achieving efficient and long-lasting therapeutic effects.
在过去十年中，人们研究了许多将基因导入皮肤的方法。然而，大多数此类方法专门针对遗传性皮肤病，且尚未产生足够的效果。此类研究的目标是开发一种方法，使基因能够轻松、高效且稳定地导入角质形成细胞，尤其是角质形成干细胞，并且转基因表达能够持续存在，而不会引发宿主免疫反应。尽管在X连锁严重联合免疫缺陷（X-SCID）基因治疗试验中意外发生了癌症，导致该研究进展放缓，但这些挫折的教训已被应用于进一步的研究。此外，结合从组织工程获得的技术，我们对干细胞知识的最新进展将为遗传性皮肤病带来新的治疗方法。本综述总结了将治疗性基因导入角质形成细胞的方法，讨论了如何提高基因转移效率，特别强调了皮肤屏障功能的破坏。最后讨论了角质形成细胞基因治疗在实现高效和持久治疗效果方面的挑战和前景。
