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.

中文翻译：

---

来自金黄色葡萄球菌（SauriCas9）的紧凑型Cas9直系同源物扩展了DNA靶向范围。

可以包装到腺相关病毒（AAV）中的紧凑型CRISPR / Cas9系统在基因治疗方面具有广阔的前景。不幸的是，当前可用的小Cas9核酸酶显示低活性或需要长的原间隔子相邻基序（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）中鉴定了一个小的Cas9直系同源物，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，可以包装到AAV中进行基因组编辑。此外，可以通过将SauriCas9融合到胞苷和腺嘌呤脱氨酶中来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。