Sequence-specific prediction of the efficiencies of adenine and cytosine base editors

Myungjae Song, Hui Kwon Kim, Sungtae Lee, Younggwang Kim, Sang Yeon Seo, Jinman Park, Jae Woo Choi, Hyewon Jang, Jeong Hong Shin, Seonwoo Min, Zhejiu Quan, Ji Hun Kim, Hoon Chul Kang, Sungroh Yoon, Hyongbum Henry Kim

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Base editors, including adenine base editors (ABEs)1 and cytosine base editors (CBEs)2,3, are widely used to induce point mutations. However, determining whether a specific nucleotide in its genomic context can be edited requires time-consuming experiments. Furthermore, when the editable window contains multiple target nucleotides, various genotypic products can be generated. To develop computational tools to predict base-editing efficiency and outcome product frequencies, we first evaluated the efficiencies of an ABE and a CBE and the outcome product frequencies at 13,504 and 14,157 target sequences, respectively, in human cells. We found that there were only modest asymmetric correlations between the activities of the base editors and Cas9 at the same targets. Using deep-learning-based computational modeling, we built tools to predict the efficiencies and outcome frequencies of ABE- and CBE-directed editing at any target sequence, with Pearson correlations ranging from 0.50 to 0.95. These tools and results will facilitate modeling and therapeutic correction of genetic diseases by base editing.

Original languageEnglish
Pages (from-to)1037-1043
Number of pages7
JournalNature Biotechnology
Issue number9
Publication statusPublished - 2020 Sept 1

Bibliographical note

Funding Information:
We are grateful to W. Wurst and O. Ortiz for providing the split-Cas9 plasmids. We thank J. Lee, J. Kweon, Y. Kim and G. Yu for technical assistance. We are also grateful to S. Park and Y. Kim for assisting with the experiments. This work was supported in part by the National Research Foundation of Korea (grant nos. 2017R1A2B3004198 (H.K.), 2017M3A9B4062403 (H.K.) and 2018R1A5A2025079 (H.K.)), Brain Korea 21 Plus Project (Yonsei University College of Medicine), Yonsei University Future-leading Research Initiative of 2015 (Challenge; grant no. RMS2 2015-22-0092) and the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (grant nos. HI17C0676 (H.K.) and HI16C1012 (H.K.)).

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering


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