Genodermatoses represent a large group of inherited skin disorders encompassing clinically-heterogeneous conditions that manifest in the skin and other organs. Depending on disease variant, associated clinical manifestations and secondary complications can severely impact patients’ quality of life and currently available treatments are transient and not curative. Multiple emerging approaches using CRISPR-based technologies offer promising prospects for therapy. Here, we explore current advances and challenges related to gene editing in rare skin diseases, including different strategies tailored to mutation type and structural organization of the affected gene, considerations for and applications, the critical issue of delivery into the skin, and immune aspects of therapy. Against the backdrop of a landmark FDA approval for the first re-dosable gene replacement therapy for a rare genetic skin disorder, gene editing approaches are inching closer to the clinics and the possibility of a local permanent cure for patients affected by these disorders.

中文翻译：

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罕见皮肤病基因编辑相关的挑战和进展


遗传性皮肤病代表一大类遗传性皮肤病，包括皮肤和其他器官中表现的临床异质性疾病。根据疾病变异，相关的临床表现和继发并发症可能会严重影响患者的生活质量，而目前可用的治疗方法是短暂的且无法治愈。多种使用基于 CRISPR 技术的新兴方法为治疗提供了广阔的前景。在这里，我们探讨了与罕见皮肤病基因编辑相关的当前进展和挑战，包括针对受影响基因的突变类型和结构组织量身定制的不同策略、考虑因素和应用、递送到皮肤的关键问题以及基因编辑的免疫方面治疗。在 FDA 批准首个针对罕见遗传性皮肤病的可重复给药基因替代疗法具有里程碑意义的背景下，基因编辑方法正一步步接近临床，并有可能为受这些疾病影响的患者提供局部永久治愈。