Kim, J. S. & Chen, J. Base editing of organellar DNA with programmable deaminases. Nat. Rev. Mol. Cell Biol. 25, 34–45 (2024).
Barrera-Paez, J. D. & Moraes, C. T. Mitochondrial genome engineering coming-of-age. Trends Genet. 38, 869–880 (2022).
Silva-Pinheiro, P. & Minczuk, M. The potential of mitochondrial genome engineering. Nat. Rev. Genet. 23, 199–214 (2022).
Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420–424 (2016).
Gaudelli, N. M. et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551, 464–471 (2017).
Li, X. et al. Base editing with a Cpf1–cytidine deaminase fusion. Nat. Biotechnol. 36, 324–327 (2018).
Wang, X. et al. Efficient base editing in methylated regions with a human APOBEC3A–Cas9 fusion. Nat. Biotechnol. 36, 946–949 (2018).
Yang, B., Yang, L. & Chen, J. Development and application of base editors. CRISPR J. 2, 91–104 (2019).
Yang, L. & Chen, J. A tale of two moieties: rapidly evolving CRISPR/Cas-based genome editing. Trends Biochem. Sci. 45, 874–888 (2020).
Richter, M. F. et al. Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat. Biotechnol. 38, 883–891 (2020).
Wang, X. et al. Cas12a base editors induce efficient and specific editing with low DNA damage response. Cell Rep. 31, 107723 (2020).
Wang, L. et al. Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations. Nat. Cell Biol. 23, 552–563 (2021).
Han, W. et al. Design and application of the transformer base editor in mammalian cells and mice. Nat. Protoc. 18, 3194–3228 (2023).
Cho, S. I. et al. Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases. Cell 185, 1764–1776 (2022).
Mok, B. Y. et al. A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature 583, 631–637 (2020).
Guo, J. et al. A DddA ortholog-based and transactivator-assisted nuclear and mitochondrial cytosine base editors with expanded target compatibility. Mol. Cell 83, 1710–1724 (2023).
Huang, J. et al. Discovery of deaminase functions by structure-based protein clustering. Cell 186, 3182–3195 (2023).
Mi, L. et al. DddA homolog search and engineering expand sequence compatibility of mitochondrial base editing. Nat. Commun. 14, 874 (2023).
Lim, K., Cho, S. I. & Kim, J. S. Nuclear and mitochondrial DNA editing in human cells with zinc finger deaminases. Nat. Commun. 13, 366 (2022).
Willis, J. C. W., Silva-Pinheiro, P., Widdup, L., Minczuk, M. & Liu, D. R. Compact zinc finger base editors that edit mitochondrial or nuclear DNA in vitro and in vivo. Nat. Commun. 13, 7204 (2022).
Sun, H. et al. Developing mitochondrial base editors with diverse context compatibility and high fidelity via saturated spacer library. Nat. Commun. 14, 6625 (2023).
Fauser, F. et al. Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells. Nat. Commun. 15, 1181 (2024).
Yin, L., Shi, K. & Aihara, H. Structural basis of sequence-specific cytosine deamination by double-stranded DNA deaminase toxin DddA. Nat. Struct. Mol. Biol. 30, 1153–1159 (2023).
Krokan, H. E. & Bjoras, M. Base excision repair. Cold Spring Harb. Perspect. Biol. 5, a012583 (2013).
Beard, W. A., Horton, J. K., Prasad, R. & Wilson, S. H. Eukaryotic base excision repair: new approaches shine light on mechanism. Annu. Rev. Biochem. 88, 137–162 (2019).
Devchand, P. R., McGhee, J. D. & van de Sande, J. H. Uracil-DNA glycosylase as a probe for protein–DNA interactions. Nucleic Acids Res. 21, 3437–3443 (1993).
Carter, R. J. & Parsons, J. L. Base excision repair, a pathway regulated by posttranslational modifications. Mol. Cell. Biol. 36, 1426–1437 (2016).
Lei, L. et al. APOBEC3 induces mutations during repair of CRISPR–Cas9-generated DNA breaks. Nat. Struct. Mol. Biol. 25, 45–52 (2018).
Georgiadis, P., Polychronaki, N. & Kyrtopoulos, S. A. Progress in high-throughput assays of MGMT and APE1 activities in cell extracts. Mutat. Res. 736, 25–32 (2012).
Chen, J., Miller, B. F. & Furano, A. V. Repair of naturally occurring mismatches can induce mutations in flanking DNA. eLife 3, e02001 (2014).
Keijzers, G., Liu, D. & Rasmussen, L. J. Exonuclease 1 and its versatile roles in DNA repair. Crit. Rev. Biochem. Mol. Biol. 51, 440–451 (2016).
Cymerman, I. A., Chung, I., Beckmann, B. M., Bujnicki, J. M. & Meiss, G. EXOG, a novel paralog of endonuclease G in higher eukaryotes. Nucleic Acids Res. 36, 1369–1379 (2008).
Yang, C. et al. Structural insights into DNA degradation by human mitochondrial nuclease MGME1. Nucleic Acids Res. 46, 11075–11088 (2018).
Zheng, L. et al. Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates. Mol. Cell 32, 325–336 (2008).
Mok, B. Y. et al. CRISPR-free base editors with enhanced activity and expanded targeting scope in mitochondrial and nuclear DNA. Nat. Biotechnol. 40, 1378–1387 (2022).
Mok, Y. G. et al. Base editing in human cells with monomeric DddA–TALE fusion deaminases. Nat. Commun. 13, 4038 (2022).
Yi, Z. et al. Strand-selective base editing of human mitochondrial DNA using mitoBEs. Nat. Biotechnol. 42, 498–509 (2024).
Hu, J. et al. Strand-preferred base editing of organellar and nuclear genomes using CyDENT. Nat. Biotechnol. 42, 936–945 (2024).
Cho, S. I. et al. Engineering TALE-linked deaminases to facilitate precision adenine base editing in mitochondrial DNA. Cell 187, 95–109 (2024).
Corona, P. et al. A novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients. Ann. Neurol. 49, 106–110 (2001).
Lebon, S. et al. Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency. J. Med. Genet. 40, 896–899 (2003).
Lei, Z. et al. Mitochondrial base editor induces substantial nuclear off-target mutations. Nature 606, 804–811 (2022).
Alexeyev, M., Shokolenko, I., Wilson, G. & LeDoux, S. The maintenance of mitochondrial DNA integrity–critical analysis and update. Cold Spring Harb. Perspect. Biol. 5, a012641 (2013).
Fontana, G. A. & Gahlon, H. L. Mechanisms of replication and repair in mitochondrial DNA deletion formation. Nucleic Acids Res. 48, 11244–11258 (2020).
Reddy, P. et al. Selective elimination of mitochondrial mutations in the germline by genome editing. Cell 161, 459–469 (2015).
Peeva, V. et al. Linear mitochondrial DNA is rapidly degraded by components of the replication machinery. Nat. Commun. 9, 1727 (2018).
Lapinaite, A. et al. DNA capture by a CRISPR–Cas9-guided adenine base editor. Science 369, 566–571 (2020).
Nilsen, H. et al. Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication. Mol. Cell 5, 1059–1065 (2000).
Raguram, A., Banskota, S. & Liu, D. R. Therapeutic in vivo delivery of gene editing agents. Cell 185, 2806–2827 (2022).
Yang, J. et al. ULtiMATE system for rapid assembly of customized TAL effectors. PLoS ONE 8, e75649 (2013).
Wang, L. et al. Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor. Cell Res. 27, 1289–1292 (2017).
McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).
Wilm, A. et al. LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets. Nucleic Acids Res. 40, 11189–11201 (2012).
Kim, S. et al. Strelka2: fast and accurate calling of germline and somatic variants. Nat. Methods 15, 591–594 (2018).
Lee, S., Lee, H., Baek, G. & Kim, J. S. Precision mitochondrial DNA editing with high-fidelity DddA-derived base editors. Nat. Biotechnol. 41, 378–386 (2023).