Wang Feizuo, Ma Shengsheng, Zhang Senfeng, Ji Quanquan, Hu Chunyi
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.
Sci China Life Sci. 2024 Dec;67(12):2563-2574. doi: 10.1007/s11427-023-2566-8. Epub 2024 Jul 12.
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.
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。
