A compact Cas9 ortholog from Staphylococcus Auricularis (SauriCas9) expands the DNA targeting scope

被引:113
作者
Hu, Ziying [1 ]
Wang, Shuai [1 ]
Zhang, Chengdong [1 ]
Gao, Ning [1 ]
Li, Miaomiao [1 ]
Wang, Deqian [1 ]
Wang, Daqi [1 ]
Liu, Dong [2 ]
Liu, Huihui [3 ]
Ong, Sang-Ging [4 ,5 ]
Wang, Hongyan [1 ]
Wang, Yongming [1 ,2 ,6 ]
机构
[1] Fudan Univ, Sch Life Sci, Zhongshan Hosp, Obstet & Gynecol Hosp,State Key Lab Genet Engn, Shanghai, Peoples R China
[2] Nantong Univ, Coinnovat Ctr Neuroregenerat, Jiangsu Key Lab Neuroregenerat, Sch Life Sci, Nantong, Peoples R China
[3] Chinese Acad Forestry, Expt Ctr Forestry North China, Beijing, Peoples R China
[4] Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA
[5] Univ Illinois, Coll Med, Dept Med, Div Cardiol, Chicago, IL USA
[6] Shanghai Engn Res Ctr Ind Microorganisms, Shanghai, Peoples R China
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
GENOMIC DNA; DUAL-RNA; BASE; ENDONUCLEASE; CRISPR-CAS9; CLEAVAGE;
D O I
10.1371/journal.pbio.3000686
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Compact CRISPR/Cas9 systems that can be packaged into an adeno-associated virus (AAV) hold great promise for gene therapy. Unfortunately, currently available small Cas9 nucleases either display low activity or require a long protospacer adjacent motif (PAM) sequence, limiting their extensive applications. Here, we screened a panel of Cas9 nucleases and identified a small Cas9 ortholog from Staphylococcus auricularis (SauriCas9), which recognizes a simple NNGG PAM, displays high activity for genome editing, and is compact enough to be packaged into an AAV for genome editing. Moreover, the conversion of adenine and cytosine bases can be achieved by fusing SauriCas9 to the cytidine and adenine deaminase. Therefore, SauriCas9 holds great potential for both basic research and clinical applications.
引用
收藏
页数:18
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