Computer-aided engineering of CRISPR-Cas proteins for enhanced human genome editing

作     者：Yangcan Chen Yanping Hu Shengqiu Luo Xinge Wang Bangwei Mao Yi Chen Jing Xu Zhikun Li Qi Zhou Wei Li 

作者机构：State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of SciencesBeijing 100049China Institute for Stem Cell and Regenerative MedicineChinese Academy of SciencesBeijing 100101China Bejing Institute for Stem Cell and Regenerative MedicineBeijing 100101China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2023年第66卷第4期

页      面：883-886页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 08[工学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

基　　金：supported by the National Key Research and Development Program(2020YFA0707900,2018YFE0201100,2019YFA0110800 to W.L.,2018YFA0108400,2019YFA0903800 to Q.Z.) the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030403 to W.L.) the National Natural Science Foundation of China(31621004 to Q.Z.and W.L.) the CAS Project for Young Scientists in Basic Research(YSBR-012 to W.L.) 

主　　题：rational editor editing 

摘      要：Dear *** remarkably diversified CRISPR-Cas systems in nature have provided unlimited valuable resources to develop genome editing tools that are revolutionizing the fields of biotechnology and ***,due to their microbial origin,the activity of most naturally occurring CRISPR-Cas nucleases is relatively poor in mammalian cells(Ran et al.,2015).Thus,improving the mammalian genome editing efficiency becomes the priority for harnessing more CRISPRCas systems for widespread *** protein engineering serves as a powerful approach to enhance the catalytic activity of ***,this approach largely relies on proteinic three-dimension(3D)structure information as guide for *** fact is that of the large numbers of the CRISPR-Cas systems discovered in recent years,only a small number of them with the 3D structures were *** bypass this limitation,here,we report an efficient and simple strategy for rational engineering of Cas nucleases without the need of 3D structure information and successfully optimized nucleases from Cas9 and Cas12 families.