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通过创新策略和理念推进CRISPR碱基编辑技术。

Advancing CRISPR base editing technology through innovative strategies and ideas.

作者信息

Fan Xiongwei, Lei Yang, Wang Liren, Wu Xiushan, Li Dali

机构信息

The Center for Heart Development, College of Life Science, Hunan Normal University, Changsha, 410081, China.

Shanghai Frontiers Science Research Base of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.

出版信息

Sci China Life Sci. 2025 Mar;68(3):610-627. doi: 10.1007/s11427-024-2699-5. Epub 2024 Sep 2.

Abstract

The innovation of CRISPR/Cas gene editing technology has developed rapidly in recent years. It is widely used in the fields of disease animal model construction, biological breeding, disease diagnosis and screening, gene therapy, cell localization, cell lineage tracking, synthetic biology, information storage, etc. However, developing idealized editors in various fields is still a goal for future development. This article focuses on the development and innovation of non-DSB editors BE and PE in the platform-based CRISPR system. It first explains the application of ideas for improvement such as "substitution", "combination", "adaptation", and "adjustment" in BE and PE development and then catalogues the ingenious inversions and leaps of thought reflected in the innovations made to CRISPR technology. It will then elaborate on the efforts currently being made to develop small editors to solve the problem of AAV overload and summarize the current application status of editors for in vivo gene modification using AAV as a delivery system. Finally, it summarizes the inspiration brought by CRISPR/Cas innovation and assesses future prospects for development of an idealized editor.

摘要

近年来,CRISPR/Cas基因编辑技术的创新发展迅速。它广泛应用于疾病动物模型构建、生物育种、疾病诊断与筛查、基因治疗、细胞定位、细胞谱系追踪、合成生物学、信息存储等领域。然而,在各个领域开发理想化的编辑器仍然是未来发展的一个目标。本文重点介绍基于平台的CRISPR系统中非双链断裂编辑器BE和PE的发展与创新。它首先解释了“替换”“组合”“适配”和“调整”等改进思路在BE和PE开发中的应用,然后梳理了CRISPR技术创新中体现的巧妙反转和思维飞跃。接着,它将详细阐述目前为开发小型编辑器以解决AAV过载问题所做的努力,并总结以AAV作为递送系统进行体内基因修饰的编辑器的当前应用状况。最后,它总结了CRISPR/Cas创新带来的启示,并评估了理想化编辑器未来的发展前景。

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