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By fusing deaminases with Cas9 nickase (nCas9), various cytosine and adenine base editors (CBEs and ABEs) have been successfully developed that can efficiently induce nucleotide conversions and install pathogenic single nucleotide variants (SNVs) in cultured cells and animal models. However, the applications of BEs are frequently limited by the specific protospacer adjacent motif (PAM) sequences and protein sizes. To expand the toolbox for BEs that can recognize novel PAM sequences, we cloned a Cas9 ortholog from <jats:italic>Streptococcus sinensis<\/jats:italic> (named as SsiCas9) with a smaller size and constructed it into APOBEC1\u2010 or APOBEC3A\u2010composed CBEs and TadA or TadA*\u2010composed ABEs, which yield high editing efficiencies, low off\u2010targeting activities, and low indel rates in human cells. Compared to PAMless SpRY Cas9\u2010composed BE4max, SsiCas9\u2010mediated BE4max displayed higher editing efficiencies for targets with \u201cNNAAAA\u201d PAM sequences. Moreover, SsiCas9\u2010mediated BE4max induced highly efficient C\u2010to\u2010T conversions in the mouse <jats:italic>Ar<\/jats:italic> gene (R841C) to introduce a human androgen resistance syndrome\u2010related mutation (<jats:italic>AR<\/jats:italic> R820C) in early mouse embryos. Thus, we developed novel BEs mediated by SsiCas9, expanded the toolbox for base conversions, and broadened the range of editable genomes in vitro and in vivo.<\/jats:p>","DOI":"10.1002\/biot.202200533","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T15:28:15Z","timestamp":1676647695000},"source":"Crossref","is-referenced-by-count":3,"title":["Cas9\u2010orthologue\u2010mediated cytosine and adenine base editors recognizing NNAAAA PAM sequences"],"prefix":"10.1002","volume":"18","author":[{"given":"Min","family":"Li","sequence":"first","affiliation":[{"name":"Precise Genome Engineering Center, School of Life Sciences Guangzhou University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Precise Genome Engineering Center, School of Life Sciences Guangzhou University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Xue","sequence":"additional","affiliation":[{"name":"Precise Genome Engineering Center, School of Life Sciences Guangzhou University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingli","family":"Zhong","sequence":"additional","affiliation":[{"name":"Precise Genome Engineering Center, School of Life Sciences Guangzhou University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Institute of Precision Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiankui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Precise Genome Engineering Center, School of Life Sciences Guangzhou University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhua","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Life Sciences Guangzhou University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-5868","authenticated-orcid":false,"given":"Yunbo","family":"Qiao","sequence":"additional","affiliation":[{"name":"Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Institute of Precision Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-120417-031501"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12438-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2422"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03145-z"},{"key":"e_1_2_9_6_1","first-page":"121","article-title":"Therapeutic genome editing: Prospects and challenges","volume":"21","author":"Cox D. 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