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基于 CRISPR 的表观基因组编辑:机制与应用。

CRISPR-based epigenome editing: mechanisms and applications.

机构信息

Department of Life Sciences, College of Science & General Studies, Alfaisal University, Riyadh, 11533, Kingdom of Saudi Arabia.

Medical Teaching Insitute, Ayub Teaching Hospital, Abbottabad, 22020, Pakistan.

出版信息

Epigenomics. 2023 Nov;15(21):1137-1155. doi: 10.2217/epi-2023-0281. Epub 2023 Nov 22.

Abstract

Epigenomic anomalies contribute significantly to the development of numerous human disorders. The development of epigenetic research tools is essential for understanding how epigenetic marks contribute to gene expression. A gene-editing technique known as CRISPR (clustered regularly interspaced short palindromic repeats) typically targets a particular DNA sequence using a guide RNA (gRNA). CRISPR/Cas9 technology has been remodeled for epigenome editing by generating a 'dead' Cas9 protein (dCas9) that lacks nuclease activity and juxtaposing it with an epigenetic effector domain. Based on fusion partners of dCas9, a specific epigenetic state can be achieved. CRISPR-based epigenome editing has widespread application in drug screening, cancer treatment and regenerative medicine. This paper discusses the tools developed for CRISPR-based epigenome editing and their applications.

摘要

表观基因组异常对许多人类疾病的发展有重大影响。开发表观遗传研究工具对于理解表观遗传标记如何影响基因表达至关重要。一种名为 CRISPR(成簇的规律间隔短回文重复序列)的基因编辑技术通常使用指导 RNA(gRNA)靶向特定的 DNA 序列。CRISPR/Cas9 技术已被改造成用于表观基因组编辑的技术,通过生成一种缺乏核酸酶活性的“失活”Cas9 蛋白(dCas9),并将其与表观遗传效应结构域并置。基于 dCas9 的融合伙伴,可以实现特定的表观遗传状态。基于 CRISPR 的表观基因组编辑在药物筛选、癌症治疗和再生医学中有广泛的应用。本文讨论了为基于 CRISPR 的表观基因组编辑开发的工具及其应用。

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