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.
Bibliographical noteFunding 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.
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
ASJC Scopus subject areas
- Applied Microbiology and Biotechnology
- Molecular Medicine
- Biomedical Engineering