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. 2022 Dec 22;13:7867. doi: 10.1038/s41467-022-35640-4

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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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Fig. 1 — a Schematics for assessing chromosomal structural variations induced by dual-AAV-delivered SpCas9 in the mouse eye. b Editing efficiency for Vegfa-sg1 in mouse eye at 2-, 4- and 12-weeks post-transfection detected by PEM-seq. Error bars, mean ± SD (For 2-, 4-, and 12-weeks post-PBS injection mice, n = 8, 6, 6, respectively; for 2-, 4-, and 12-weeks post-AAV injection mice, n = 3, 3, 5, respectively). c Circos plot indicating translocations among on-target and off-targets of Vegfa-sg1 in mouse eye detected by PEM-seq. DNA sequences for on-target and off-targets of Vegfa-sg1 are shown in the table. Mismatches of DNA sequences between on-target and off-targets are in red. d Percentages for off-target translocations (left) and general translocations (right) in mouse eye cloned from Vegfa-sg1 at 2-, 4- and 12-weeks post-transfection detected by PEM-seq. Error bars, mean ± SD (For 2-, 4-, and 12-weeks post-AAV injection mice, n = 3, 3, 6, respectively). e Percentages of AAV integrations at Vegfa-sg2 normalized to editing events at 2-, 4- and 12-weeks post-transfection detected by PEM-seq. Error bars, mean ± SD (For 2-, 4-, and 12-weeks post-AAV injection mice, n = 3, 3, 6, respectively).