A compact Cas9 ortholog from Staphylococcus Auricularis (SauriCas9) expands the DNA targeting scope
A compact Cas9 ortholog from Staphylococcus Auricularis (SauriCas9) expands the DNA targeting scope
复制标题
来自耳廓葡萄球菌 (SauriCas9) 的紧凑型 Cas9 直向同源物扩大了 DNA 靶向范围
DOI：
10.1371/journal.pbio.3000686
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发表时间：
2020-03-01
期刊：
影响因子：
9.8
通讯作者：
Wang, Yongming
中科院分区：
文献类型：
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作者：
Hu, Ziying;Wang, Shuai;Wang, Yongming
紧凑的CRISPR/Cas9系统可以包装成腺相关病毒(AAV)，为基因治疗带来了巨大的希望。遗憾的是，目前可用的小分子Cas9核酸酶要么活性低，要么需要长的邻接基序(PAM)序列，限制了它们的广泛应用。在这里，我们筛选了一组Cas9核酸酶，并从金黄色葡萄球菌(SauriCas9)中鉴定出一个小的Cas9同源基因，它识别简单的NNGG PAM，对基因组编辑显示出高活性，并且足够紧凑，可以包装成AAV进行基因组编辑。此外，通过将SauriCas9融合到胞苷和腺嘌呤脱氨酶中，可以实现腺嘌呤和胞嘧啶碱基的转化。因此，SauriCas9在基础研究和临床应用方面都具有巨大的潜力。
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.