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. 2022 Feb 8;13:750. doi: 10.1038/s41467-022-28358-w

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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. 3 — a Scheme of in vivo experiments with adult mice. The DdCBE-Nd3-9577-1 monomers (see Fig. 2), and their catalytically inactive versions, were encoded in separate AAV genomes, encapsidated in AAV9.45 then simultaneously administered by tail-vein (TV) injection at 1 × 10¹² vg/mouse of each monomer. Animals were sacrificed either 3 or 24-weeks post-injection and their cardiac tissue was examined for mtDNA editing. b, e Editing of mouse MT-Nd3 with DdCBE in mouse heart at 3-weeks (b) or 24-weeks (e) post-injection, analyzed by Sanger sequencing. Potential editing sites are indicated in purple. c, f The NGS analysis of the DdCBE editing within the targeted region in adult mouse hearts at 3 weeks (c) or 24 weeks (f) after injection. Bars represent the mean (n = 2). Source data are provided as a Source Data file. d, g The distribution of NGS reads containing m.9576 G (C₁₂) or m.9577 G (C₁₃) edits at 3 weeks (d) or 24 weeks (g) after injection. The G40K reads contain both m.9576 G > A (C₁₂ > T₁₂) and m.9577 G > A (C₁₃ > T₁₃) mutations, G40E reads contain only the m.9577 G > A (C₁₃ > T₁₃) mutation, while G40* reads contain only the m.9576 G > A (C₁₂ > T₁₂) mutation. Source data are provided as a Source Data file.