March Oliver P, Reichelt Julia, Koller Ulrich
EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Exp Physiol. 2018 Apr 1;103(4):449-455. doi: 10.1113/EP086044. Epub 2017 Mar 31.
What is the topic of this review? This review concerns current gene editing strategies for blistering skin diseases with respect to individual genetic constellations and distinct conditions. What advances does it highlight? Specificity and safety dominate the discussion of gene editing applications for gene therapy, where a number of tools are implemented. Recent developments in this rapidly progressing field pose further questions regarding which tool is best suited for each particular use. The current treatment of inherited blistering skin diseases, such as epidermolysis bullosa (EB), is largely restricted to wound care and pain management. More effective therapeutic strategies are urgently required, and targeting the genetic basis of these severe diseases is now within reach. Here, we describe current gene editing tools and their potential to correct gene function in monogenetic blistering skin diseases. We present the features of the most frequently used gene editing techniques, transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), determining their preferential application for specific genetic conditions, including the type of mutational inheritance, the targeting site within the gene or the possibility to target the mutation specifically. Both tools have traits beneficial in specific situations. Promising developments in the field engender gene editing as a potentially powerful therapeutic option for future clinical applications.
本综述的主题是什么？本综述涉及针对个体遗传构成和不同病症的水疱性皮肤病的当前基因编辑策略。它突出了哪些进展？特异性和安全性主导了基因治疗中基因编辑应用的讨论，其中采用了多种工具。在这个快速发展的领域中的最新进展引发了关于哪种工具最适合每种特定用途的进一步问题。遗传性水疱性皮肤病，如大疱性表皮松解症（EB），目前的治疗主要局限于伤口护理和疼痛管理。迫切需要更有效的治疗策略，而针对这些严重疾病的遗传基础目前已触手可及。在此，我们描述了当前的基因编辑工具及其在单基因水疱性皮肤病中纠正基因功能的潜力。我们介绍了最常用的基因编辑技术——转录激活样效应物核酸酶（TALEN）和成簇规律间隔短回文重复序列/CRISPR相关蛋白9（CRISPR/Cas9）的特点，确定它们在特定遗传条件下的优先应用，包括突变遗传类型、基因内的靶向位点或特异性靶向突变的可能性。这两种工具在特定情况下都有有益的特性。该领域有前景的进展使基因编辑成为未来临床应用中一种潜在的强大治疗选择。
