Adenine base editors catalyze cytosine conversions in human cells

Adenine base editors comprise an adenosine deaminase, evolved in vitro, and a Cas9 nickase. Here, we show that in addition to converting adenine to guanine, adenine base editors also convert cytosine to guanine or thymine in a narrow editing window (positions 5–7) and in a confined TC*N sequence con...

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Published inNature biotechnology Vol. 37; no. 10; pp. 1145 - 1148
Main Authors Kim, Heon Seok, Jeong, You Kyeong, Hur, Junho K, Kim, Jin-Soo, Bae, Sangsu
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.10.2019
Nature Publishing Group
Subjects
631/1647/1511
631/1647/1513/1967/3196
Adenine
Adenosine
Adenosine deaminase
Agriculture
Bioinformatics
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Cytosine
Editing
Guanine
Letter
Life Sciences
Thymine
South Korea
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Summary:Adenine base editors comprise an adenosine deaminase, evolved in vitro, and a Cas9 nickase. Here, we show that in addition to converting adenine to guanine, adenine base editors also convert cytosine to guanine or thymine in a narrow editing window (positions 5–7) and in a confined TC*N sequence context. Adenine base editor–induced cytosine substitutions occur independently of adenosine conversions with an efficiency of up to 11.2% and reduce the number of suitable targeting sites for high-specificity base editing. In addition to causing A-to-G base transitions, adenine base editors also cause C base substitutions
Bibliography:ObjectType-Article-1
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ISSN:1087-0156
1546-1696
DOI:10.1038/s41587-019-0254-4