Rees, H. A. & Liu, D. R. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19, 770–788 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, L. et al. Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor. Cell Res. 27, 1289–1292 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kurt, I. C. et al. CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells. Nat. Biotechnol. 39, 41–46 (2021).

Article  CAS  PubMed  Google Scholar 

Zhao, D. et al. Glycosylase base editors enable C-to-A and C-to-G base changes. Nat. Biotechnol. 39, 35–40 (2021).

Article  CAS  PubMed  Google Scholar 

Koblan, L. W. et al. Efficient C·G-to-G·C base editors developed using CRISPRi screens, target-library analysis, and machine learning. Nat. Biotechnol. 39, 1414–1425 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, L. et al. Programmable C:G to G:C genome editing with CRISPR-Cas9-directed base excision repair proteins. Nat. Commun. 12, 1384 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zuo, E. et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science 364, 289–292 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin, S. et al. Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice. Science 364, 292–295 (2019).

Article  CAS  PubMed  Google Scholar 

Zhou, C. et al. Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis. Nature 571, 275–278 (2019).

Article  CAS  PubMed  Google Scholar 

Grunewald, J. et al. Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569, 433–437 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gehrke, J. M. et al. An APOBEC3A-Cas9 base editor with minimized bystander and off-target activities. Nat. Biotechnol. 36, 977–982 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, Y. B. et al. Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions. Nat. Biotechnol. 35, 371–376 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, H. S., Jeong, Y. K., Hur, J. K., Kim, J. S. & Bae, S. Adenine base editors catalyze cytosine conversions in human cells. Nat. Biotechnol. 37, 1145–1148 (2019).

Article  CAS  PubMed  Google Scholar 

Grunewald, J. et al. CRISPR DNA base editors with reduced RNA off-target and self-editing activities. Nat. Biotechnol. 37, 1041–1048 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, L. et al. Engineering precise adenine base editor with infinitesimal rates of bystander mutations and off-target editing. Nat. Chem. Biol. https://doi.org/10.1038/s41589-022-01163-8 (2022).

Lapinaite, A. et al. DNA capture by a CRISPR-Cas9-guided adenine base editor. Science 369, 566–571 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jeong, Y. K. et al. Adenine base editor engineering reduces editing of bystander cytosines. Nat. Biotechnol. 39, 1426–1433 (2021).

Article  CAS  PubMed  Google Scholar 

Tan, J., Zhang, F., Karcher, D. & Bock, R. Engineering of high-precision base editors for site-specific single nucleotide replacement. Nat. Commun. 10, 439 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Thuronyi, B. W. et al. Continuous evolution of base editors with expanded target compatibility and improved activity. Nat. Biotechnol. 37, 1070–1079 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nishimasu, H. et al. Engineered CRISPR-Cas9 nuclease with expanded targeting space. Science 361, 1259–1262 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang, X. et al. Increasing the efficiency and targeting range of cytidine base editors through fusion of a single-stranded DNA-binding protein domain. Nat. Cell Biol. 22, 740–750 (2020).

Article  CAS  PubMed  Google Scholar 

Lee, S. et al. Single C-to-T substitution using engineered APOBEC3G-nCas9 base editors with minimum genome- and transcriptome-wide off-target effects. Sci. Adv. 6, eaba1773 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bae, S., Park, J. & Kim, J. S. Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Bioinformatics 30, 1473–1475 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Doman, J. L., Raguram, A., Newby, G. A. & Liu, D. R. Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors. Nat. Biotechnol. 38, 620–628 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, L. et al. Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations. Nat. Cell Biol. 23, 552–563 (2021).

Article  PubMed  Google Scholar 

Lei, Z. et al. Detect-seq reveals out-of-protospacer editing and target-strand editing by cytosine base editors. Nat. Methods 18, 643–651 (2021).

Article  CAS  PubMed  Google Scholar 

Lei, Z. et al. Mitochondrial base editor induces substantial nuclear off-target mutations. Nature 606, 804–811 (2022).

Article  CAS  PubMed  Google Scholar 

Yuan, T. et al. Optimization of C-to-G base editors with sequence context preference predictable by machine learning methods. Nat. Commun. 12, 4902 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Auer-Grumbach, M., Strasser-Fuchs, S., Robl, T., Windpassinger, C. & Wagner, K. Late onset Charcot-Marie-Tooth 2 syndrome caused by two novel mutations in the MPZ gene. Neurology 61, 1435–1437 (2003).

Article  CAS  PubMed  Google Scholar 

Rodriguez-Escudero, I. et al. A comprehensive functional analysis of PTEN mutations: implications in tumor- and autism-related syndromes. Hum. Mol. Genet. 20, 4132–4142 (2011).

Article  CAS  PubMed  Google Scholar 

Syrbe, S. et al. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy. Nat. Genet. 47, 393–399 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Esteghamat, F. et al. CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nat. Genet. 51, 1233–1243 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ropero, P. et al. Hb Johnstown [β 109 (G11) Val–>Leu]: second case described and associated for the first time with β0-thalassemia in two Spanish families. Am. J. Hematol. 65, 298–301 (2000).

Article  CAS  PubMed  Google Scholar 

Fazeli, W. et al. A TUBB6 mutation is associated with autosomal dominant non-progressive congenital facial palsy, bilateral ptosis and velopharyngeal dysfunction. Hum. Mol. Genet. 26, 4055–4066 (2017).

Article  CAS  PubMed