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. 2022 Sep 8;41(1):96–107. doi: 10.1038/s41587-022-01410-2

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 7 — (a) Adenine base editing activity of eNme2-C-ABE8e compared to SpRY-ABE8e and SpRY-HF1-ABE8e at 14 NCN/N4CN PAM-matched sites in HEK293T cells (pooled data in Fig. 3b). (b) Adenine base editing activity of eNme2-T.1-ABE8e and eNme2-T.2-ABE8e compared to SpRY-ABE8e and SpRY-HF1-ABE8e at eight NTN/N4TN PAM-matched sites in HEK293T cells (pooled data in Fig. 3c). (c) Cytosine base editing activity of eNme2-C-BE4 compared to SpRY-BE4 and SpRY-HF1-BE4 at eight NCN/N4CN PAM-matched sites in HEK293T cells (pooled data in Fig. 3d). (d) Nuclease activity of eNme2-C nuclease and eNme2-C.NR nuclease compared to SpRY nuclease and SpRY-HF1 nuclease at eight NCN/N4CN PAM-matched sites in HEK293T cells (pooled data in Fig. 3e). For (a-d), Mean±SEM is shown and reflects the average activity and standard error of n = 3 independent biological replicates measured at the maximally edited position (if applicable) within each given genomic site. (e) Pooled adenine base editing activity of eNme2-C-ABE8e compared to eNme2-C.NR-ABE8e or adenine base editors generated from reversion mutations at each of the eight RuvC/HNH domain mutations in eNme2-C at eight genomic sites in HEK293T cells. (f) Pooled nuclease activity of eNme2-C nuclease compared to eNme2-C.NR nuclease or nuclease-active variants generated from reversion mutations at each of the eight RuvC/HNH domain mutations in eNme2-C at eight genomic sites in HEK293T cells. For (e) and (f), each point represents the average of n = 3 independent biological replicates measured at the maximally edited position within each given genomic site in HEK293T cells. Mean±SEM is shown and reflects the average activity and standard error of the pooled genomic site averages.