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

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Title
Sequence-specific prediction of the efficiencies of adenine and cytosine base editors
Author(s)
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
Subject
GENOMIC DNA, ; OFF-TARGET, ; CRISPR-CAS9, ; GRADIENT, ; DESIGN, ; SGRNAS
Publication Date
2020-09
Journal
Nature Biotechnology, v.38, no.9, pp.1037 - 1043
Publisher
NATURE PUBLISHING GROUP
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. 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
URI
https://pr.ibs.re.kr/handle/8788114/8487
DOI
10.1038/s41587-020-0573-5
ISSN
1087-0156
Appears in Collections:
Center for Nanomedicine (나노의학 연구단) > 1. Journal Papers (저널논문)
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