The repurposing of RNA-programmable CRISPR systems from genome editing into epigenome editing tools is gaining pace, including in research and development efforts directed at tackling human disorders. This momentum stems from the increasing knowledge regarding the epigenetic factors and networks underlying cell physiology and disease etiology and from the growing realization that genome editing principles involving chromosomal breaks generated by programmable nucleases are prone to unpredictable genetic changes and outcomes. Hence, engineered CRISPR systems are serving as versatile DNA-targeting scaffolds for heterologous and synthetic effector domains that, via locally recruiting transcription factors and chromatin remodeling complexes, seek interfering with loss-of-function and gain-of-function processes underlying recessive and dominant disorders, respectively. Here, after providing an overview about epigenetic drugs and CRISPR-Cas-based activation and interference platforms, we cover the testing of these platforms in the context of molecular therapies for muscular dystrophies. Finally, we examine attributes, obstacles, and deployment opportunities for CRISPR-based epigenetic modulating technologies.

中文翻译：

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关于 RNA 可编程基因调控作为一组针对肌营养不良症的通用原理


RNA 可编程 CRISPR 系统从基因组编辑到表观基因组编辑工具的重新利用正在加快步伐，包括在旨在解决人类疾病的研发工作中。这种势头源于对细胞生理学和疾病病因学背后的表观遗传因子和网络的了解不断增加，以及人们越来越意识到，涉及由可编程核酸酶产生的染色体断裂的基因组编辑原理容易出现不可预测的遗传变化和结果。因此，工程化 CRISPR 系统可作为异源和合成效应结构域的多功能 DNA 靶向支架，这些效应结构域通过局部募集转录因子和染色质重塑复合物，分别寻求干扰隐性和显性疾病背后的功能丧失和功能获得过程。在这里，在概述了表观遗传药物和基于 CRISPR-Cas 的激活和干扰平台之后，我们介绍了在肌营养不良症分子疗法背景下对这些平台的测试。最后，我们研究了基于 CRISPR 的表观遗传调控技术的属性、障碍和部署机会。