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Sniper2L is a high-fidelity Cas9 variant with high activity

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Title
Sniper2L is a high-fidelity Cas9 variant with high activity
Author(s)
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
Publication Date
2023-08
Journal
Nature Chemical Biology, v.19, no.8, pp.972 - 980
Publisher
Nature Research
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. [Figure not available: see fulltext.]. © 2023, The Author(s).
URI
https://pr.ibs.re.kr/handle/8788114/13715
DOI
10.1038/s41589-023-01279-5
ISSN
1552-4450
Appears in Collections:
Center for Nanomedicine (나노의학 연구단) > 1. Journal Papers (저널논문)
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