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超越CRISPR:利用紧凑型RNA引导核酸内切酶增强基因组编辑

CRISPR beyond: harnessing compact RNA-guided endonucleases for enhanced genome editing.

作者信息

Wang Feizuo, Ma Shengsheng, Zhang Senfeng, Ji Quanquan, Hu Chunyi

机构信息

Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore.

Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117597, Singapore.

出版信息

Sci China Life Sci. 2024 Dec;67(12):2563-2574. doi: 10.1007/s11427-023-2566-8. Epub 2024 Jul 12.


DOI:10.1007/s11427-023-2566-8
PMID:39012436
Abstract

The CRISPR-Cas system, an adaptive immunity system in prokaryotes designed to combat phages and foreign nucleic acids, has evolved into a groundbreaking technology enabling gene knockout, large-scale gene insertion, base editing, and nucleic acid detection. Despite its transformative impact, the conventional CRISPR-Cas effectors face a significant hurdle-their size poses challenges in effective delivery into organisms and cells. Recognizing this limitation, the imperative arises for the development of compact and miniature gene editors to propel advancements in gene-editing-related therapies. Two strategies were accepted to develop compact genome editors: harnessing OMEGA (Obligate Mobile Element-guided Activity) systems, or engineering the existing CRISPR-Cas system. In this review, we focus on the advances in miniature genome editors based on both of these strategies. The objective is to unveil unprecedented opportunities in genome editing by embracing smaller, yet highly efficient genome editors, promising a future characterized by enhanced precision and adaptability in the genetic interventions.

摘要

CRISPR-Cas系统是原核生物中一种旨在对抗噬菌体和外来核酸的适应性免疫系统,现已发展成为一项开创性技术,可实现基因敲除、大规模基因插入、碱基编辑和核酸检测。尽管其具有变革性影响,但传统的CRISPR-Cas效应物面临一个重大障碍——它们的大小给有效递送至生物体和细胞带来了挑战。认识到这一局限性,开发紧凑和微型基因编辑器以推动基因编辑相关疗法的进展就变得势在必行。人们采用了两种策略来开发紧凑的基因组编辑器:利用OMEGA(专性移动元件引导活性)系统,或对现有的CRISPR-Cas系统进行工程改造。在这篇综述中,我们重点关注基于这两种策略的微型基因组编辑器的进展。目的是通过采用更小但高效的基因组编辑器,揭示基因组编辑中前所未有的机会,有望在未来实现基因干预中更高的精准度和适应性。

相似文献

[1]
CRISPR beyond: harnessing compact RNA-guided endonucleases for enhanced genome editing.

Sci China Life Sci. 2024-12

[2]
Revolutionizing CRISPR technology with artificial intelligence.

Exp Mol Med. 2025-7

[3]
CRISPR/Cas9-mediated genome editing in Ganoderma lucidum: recent advances and biotechnological opportunities.

World J Microbiol Biotechnol. 2025-6-25

[4]
Trojan Horse-Like Vehicles for CRISPR-Cas Delivery: Engineering Extracellular Vesicles and Virus-Like Particles for Precision Gene Editing in Cystic Fibrosis.

Hum Gene Ther. 2025-4-28

[5]
Fitness effects of CRISPR endonucleases in populations.

Elife. 2022-9-22

[6]
CRISPR/Cas genome editing in soybean: challenges and new insights to overcome existing bottlenecks.

J Adv Res. 2024-8-18

[7]
CRISPR-Based Regulation for High-Throughput Screening.

ACS Synth Biol. 2025-6-20

[8]
A comprehensive all-in-one CRISPR toolbox for large-scale screens in plants.

Plant Cell. 2025-4-2

[9]
Phage-based delivery of CRISPR-associated transposases for targeted bacterial editing.

Proc Natl Acad Sci U S A. 2025-7-29

[10]
Adenoviral vectors for in vivo delivery of CRISPR-Cas gene editors.

J Control Release. 2020-11-10

引用本文的文献

[1]
CRISPR/Cas9-mediated promoterless gene targeting reduces lysosome storage in MPS VII mice.

Sci China Life Sci. 2025-7-2

本文引用的文献

[1]
Robust miniature Cas-based transcriptional modulation by engineering Un1Cas12f1 and tethering Sso7d.

Mol Ther. 2024-4-3

[2]
Engineering a transposon-associated TnpB-ωRNA system for efficient gene editing and phenotypic correction of a tyrosinaemia mouse model.

Nat Commun. 2024-1-27

[3]
BacPE: a versatile prime-editing platform in bacteria by inhibiting DNA exonucleases.

Nat Commun. 2024-1-27

[4]
Self-delivering, chemically modified CRISPR RNAs for AAV co-delivery and genome editing in vivo.

Nucleic Acids Res. 2024-1-25

[5]
Improve meat production and virus resistance by simultaneously editing multiple genes in livestock using Cas12i.

Sci China Life Sci. 2024-3

[6]
Diversity, evolution, and classification of the RNA-guided nucleases TnpB and Cas12.

Proc Natl Acad Sci U S A. 2023-11-28

[7]
Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes.

Nucleic Acids Res. 2023-12-11

[8]
Reprogramming an RNA-guided archaeal TnpB endonuclease for genome editing.

Cell Discov. 2023-11-11

[9]
Split complementation of base editors to minimize off-target edits.

Nat Plants. 2023-11

[10]
New faces of prokaryotic mobile genetic elements: guide RNAs link transposition with host defense mechanisms.

Curr Opin Syst Biol. 2023-12

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