Adenine base editor engineering reduces editing of bystander cytosines

You Kyeong Jeong, Seok Hoon Lee, Gue Ho Hwang, Sung Ah Hong, Se eun Park, Jin Soo Kim, Jae Sung Woo, Sangsu Bae

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Adenine base editors (ABEs) catalyze specific A-to-G conversions at genomic sites of interest. However, ABEs also induce cytosine deamination at the target site. To reduce the cytosine editing activity, we engineered a commonly used adenosine deaminase, TadA7.10, and found that ABE7.10 with a D108Q mutation in TadA7.10 exhibited tenfold reduced cytosine deamination activity. The D108Q mutation also reduces cytosine deamination activity in two recently developed high-activity versions of ABE, ABE8e and ABE8s, and is compatible with V106W, a mutation that reduces off-target RNA editing. ABE7.10 containing a P48R mutation displayed increased cytosine deamination activity and a substantially reduced adenine editing rate, yielding a TC-specific base editing tool for TC-to-TT or TC-to-TG conversions that broadens the utility of base editors.

Original languageEnglish
JournalNature Biotechnology
DOIs
StateAccepted/In press - 2021

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