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Sniper2L is a high-fidelity Cas9 variant with high activity

Authors
 Young-Hoon Kim  ;  Nahye Kim  ;  Ikenna Okafor  ;  Sungchul Choi  ;  Seonwoo Min  ;  Joonsun Lee  ;  Seung-Min Bae  ;  Keunwoo Choi  ;  Janice Choi  ;  Vinayak Harihar  ;  Youngho Kim  ;  Jin-Soo Kim  ;  Benjamin P Kleinstiver  ;  Jungjoon K Lee  ;  Taekjip Ha  ;  Hyongbum Henry Kim 
Citation
 NATURE CHEMICAL BIOLOGY, : epub, 2023-03 
Journal Title
NATURE CHEMICAL BIOLOGY
ISSN
 1552-4450 
Issue Date
2023-03
Abstract
Although several high-fidelity SpCas9 variants have been reported, it has been observed that this increased specificity is associated with reduced on-target activity, limiting the applications of the high-fidelity variants when efficient genome editing is required. Here, we developed an improved version of Sniper-Cas9, Sniper2L, which represents an exception to this trade-off trend as it showed higher specificity with retained high activity. We evaluated Sniper2L activities at a large number of target sequences and developed DeepSniper, a deep learning model that can predict the activity of Sniper2L. We also confirmed that Sniper2L can induce highly efficient and specific editing at a large number of target sequences when it is delivered as a ribonucleoprotein complex. Mechanically, the high specificity of Sniper2L originates from its superior ability to avoid unwinding a target DNA containing even a single mismatch. We envision that Sniper2L will be useful when efficient and specific genome editing is required.
Full Text
https://www.nature.com/articles/s41589-023-01279-5
DOI
10.1038/s41589-023-01279-5
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyongbum(김형범) ORCID logo https://orcid.org/0000-0002-4693-738X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195312
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