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基因编辑疗法治疗遗传性皮肤病的挑战。

Challenges of Gene Editing Therapies for Genodermatoses.

机构信息

St John's Institute of Dermatology, King's College London, London SE1 9RT, UK.

出版信息

Int J Mol Sci. 2023 Jan 24;24(3):2298. doi: 10.3390/ijms24032298.

Abstract

Genodermatoses encompass a wide range of inherited skin diseases, many of which are monogenic. Genodermatoses range in severity and result in early-onset cancers or life-threatening damage to the skin, and there are few curative options. As such, there is a clinical need for single-intervention treatments with curative potential. Here, we discuss the nascent field of gene editing for the treatment of genodermatoses, exploring CRISPR-Cas9 and homology-directed repair, base editing, and prime editing tools for correcting pathogenic mutations. We specifically focus on the optimisation of editing efficiency, the minimisation off-targets edits, and the tools for delivery for potential future therapies. Honing each of these factors is essential for translating gene editing therapies into the clinical setting. Therefore, the aim of this review article is to raise important considerations for investigators aiming to develop gene editing approaches for genodermatoses.

摘要

遗传性皮肤病涵盖了广泛的范围,其中许多是单基因遗传的。遗传性皮肤病的严重程度不同,会导致早期癌症或危及生命的皮肤损伤,而且治疗选择很少。因此,临床上需要有治疗潜力的单一干预治疗方法。在这里,我们讨论了基因编辑治疗遗传性皮肤病的新兴领域,探讨了 CRISPR-Cas9 和同源定向修复、碱基编辑和 Prime 编辑工具,用于纠正致病突变。我们特别关注编辑效率的优化、减少脱靶编辑的方法,以及用于未来潜在治疗的递送工具。这些因素的优化对于将基因编辑疗法转化为临床应用至关重要。因此,本文的目的是为旨在开发遗传性皮肤病基因编辑方法的研究人员提出重要的考虑因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3873/9916788/1673f9630f19/ijms-24-02298-g001.jpg

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