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

41 Citations (Scopus)

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
Pages (from-to)1426-1433
Number of pages8
JournalNature Biotechnology
Volume39
Issue number11
DOIs
Publication statusPublished - 2021 Nov

Bibliographical note

Funding Information:
This research was supported by grants from the National Research Foundation of Korea no. 2020M3A9I4036072, no. 2020R1A6A1A06046728, no. 2021R1A2C3012908 and no. 2021M3A9H3015389 to S.B., and no. 2018R1C1B6004447 to J.-S.W.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

ASJC Scopus subject areas

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

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