Prime editing for precise and highly versatile genome manipulation

IF 39.1 1区生物学 Q1 GENETICS & HEREDITY Nature Reviews Genetics Pub Date : 2022-11-07 DOI:10.1038/s41576-022-00541-1

Peter J. Chen, David R. Liu

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引用次数: 63

Abstract

Programmable gene-editing tools have transformed the life sciences and have shown potential for the treatment of genetic disease. Among the CRISPR–Cas technologies that can currently make targeted DNA changes in mammalian cells, prime editors offer an unusual combination of versatility, specificity and precision. Prime editors do not require double-strand DNA breaks and can make virtually any substitution, small insertion and small deletion within the DNA of living cells. Prime editing minimally requires a programmable nickase fused to a polymerase enzyme, and an extended guide RNA that both specifies the target site and templates the desired genome edit. In this Review, we summarize prime editing strategies to generate programmed genomic changes, highlight their limitations and recent developments that circumvent some of these bottlenecks, and discuss applications and future directions. In this Review, Chen and Liu discuss the latest developments in prime editing systems, including improvements to their editing efficiency and capabilities, as well as diverse emerging applications in research and preclinical therapeutic studies.

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主要编辑功能，可实现精确、多功能的基因组操作。

可编程基因编辑工具改变了生命科学，并显示出治疗遗传疾病的潜力。目前，CRISPR-Cas 技术可以对哺乳动物细胞中的 DNA 进行有针对性的改变，其中，主编辑器集多功能性、特异性和精确性于一身。主编辑器不需要双链DNA断裂，几乎可以在活细胞的DNA中进行任何替换、小规模插入和小规模删除。基质编辑只需要一个融合了聚合酶的可编程缺口酶，以及一个扩展的引导 RNA，它既能指定目标位点，又能模板所需的基因组编辑。在这篇综述中，我们总结了产生程序化基因组变化的原位编辑策略，强调了它们的局限性和规避其中一些瓶颈的最新进展，并讨论了应用和未来方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Reviews Genetics 生物-遗传学

CiteScore

57.40

自引率

0.50%

发文量

113

审稿时长

6-12 weeks

期刊介绍： At Nature Reviews Genetics, our goal is to be the leading source of reviews and commentaries for the scientific communities we serve. We are dedicated to publishing authoritative articles that are easily accessible to our readers. We believe in enhancing our articles with clear and understandable figures, tables, and other display items. Our aim is to provide an unparalleled service to authors, referees, and readers, and we are committed to maximizing the usefulness and impact of each article we publish. Within our journal, we publish a range of content including Research Highlights, Comments, Reviews, and Perspectives that are relevant to geneticists and genomicists. With our broad scope, we ensure that the articles we publish reach the widest possible audience. As part of the Nature Reviews portfolio of journals, we strive to uphold the high standards and reputation associated with this esteemed collection of publications.

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