논문

게재년월 2020/11
논문제목 Prediction of the sequence-specific cleavage activity of Cas9 variants
참여교수 김형범
학술지명 NATURE BIOTECHNOLOGY
초록 Several Streptococcus pyogenes Cas9 (SpCas9) variants have been developed to improve an enzyme\'s specificity or to alter or broaden its protospacer-adjacent motif (PAM) compatibility, but selecting the optimal variant for a given target sequence and application remains difficult. To build computational models to predict the sequence-specific activity of 13 SpCas9 variants, we first assessed their cleavage efficiency at 26,891 target sequences. We found that, of the 256 possible four-nucleotide NNNN sequences, 156 can be used as a PAM by at least one of the SpCas9 variants. For the high-fidelity variants, overall activity could be ranked as SpCas9 ≥ Sniper-Cas9 > eSpCas9(1.1) > SpCas9-HF1 > HypaCas9 ≈ xCas9 >> evoCas9, whereas their overall specificities could be ranked as evoCas9 >> HypaCas9 ≥ SpCas9-HF1 ≈ eSpCas9(1.1) > xCas9 > Sniper-Cas9 > SpCas9. Using these data, we developed 16 deep-learning-based computational models that accurately predict the activity of these variants at any target sequence.
게재정보 Nat Biotechnol. 2020 Nov;38(11):1328-1336
총저자명 Nahye Kim, Hui Kwon Kim, Sungtae Lee, Jung Hwa Seo, Jae Woo Choi, Jinman Park, Seonwoo Min, Sungroh Yoon, Sung-Rae Cho, Hyongbum Henry Kim