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).
Porto, E. M., Komor, A. C., Slaymaker, I. M. & Yeo, G. W. Base editing: advances and therapeutic opportunities. Nat. Rev. Drug Discov. 19, 839–859 (2020).
Pfeiffer, L. S. & Stafforst, T. Precision RNA base editing with engineered and endogenous effectors. Nat. Biotechnol. 41, 1526–1542 (2023).
Song, J., Zhuang, Y. & Yi, C. Programmable RNA base editing via targeted modifications. Nat. Chem. Biol. 20, 277–290 (2024).
Cox, D. B. T. et al. RNA editing with CRISPR–Cas13. Science 358, 1019–1027 (2017).
Rauch, S. et al. Programmable RNA-guided RNA effector proteins built from human parts. Cell 178, 122–134 (2019).
Yi, Z. et al. Engineered circular ADAR-recruiting RNAs increase the efficiency and fidelity of RNA editing in vitro and in vivo. Nat. Biotechnol. 40, 946–955 (2022).
Katrekar, D. et al. Efficient in vitro and in vivo RNA editing via recruitment of endogenous ADARs using circular guide RNAs. Nat. Biotechnol. 40, 938–945 (2022).
Qian, Y. et al. Programmable RNA sensing for cell monitoring and manipulation. Nature 610, 713–721 (2022).
Jiang, K. et al. Programmable eukaryotic protein synthesis with RNA sensors by harnessing ADAR. Nat. Biotechnol. 41, 698–707 (2022).
Kaseniit, K. E. et al. Modular, programmable RNA sensing using ADAR editing in living cells. Nat. Biotechnol. 41, 482–487 (2022).
Reautschnig, P. et al. CLUSTER guide RNAs enable precise and efficient RNA editing with endogenous ADAR enzymes in vivo. Nat. Biotechnol. 40, 759–768 (2022).
Ojha, N., Diaz Quiroz, J. F. & Rosenthal, J. J. C. In vitro and in cellula site-directed RNA editing using the λNDD-BoxB system. Methods Enzymol. 658, 335–358 (2021).
Abudayyeh, O. O. et al. A cytosine deaminase for programmable single-base RNA editing. Science 365, 382–386 (2019).
Huang, X. et al. Programmable C-to-U RNA editing using the human APOBEC3A deaminase. EMBO J. 39, e104741 (2020).
Latifi, N., Mack, A. M., Tellioglu, I., Di Giorgio, S. & Stafforst, T. Precise and efficient C-to-U RNA base editing with SNAP-CDAR-S. Nucleic Acids Res. 51, e84 (2023).
Bhakta, S., Sakari, M. & Tsukahara, T. RNA editing of BFP, a point mutant of GFP, using artificial APOBEC1 deaminase to restore the genetic code. Sci. Rep. 10, 17304 (2020).
Han, W. et al. Programmable RNA base editing with a single gRNA-free enzyme. Nucleic Acids Res. 50, 9580–9595 (2022).
Stroppel, A. S. et al. Harnessing self-labeling enzymes for selective and concurrent A-to-I and C-to-U RNA base editing. Nucleic Acids Res. 49, e95 (2021).
Liu, Z., Jillette, N., Robson, P. & Cheng, A. W. Simultaneous multifunctional transcriptome engineering by CRISPR RNA scaffold. Nucleic Acids Res. 51, e77 (2023).
Song, J. et al. CRISPR-free, programmable RNA pseudouridylation to suppress premature termination codons. Mol. Cell 83, 139–155 (2023).
Adachi, H. et al. Targeted pseudouridylation: an approach for suppressing nonsense mutations in disease genes. Mol. Cell 83, 637–651 (2023).
Luo, N. et al. Near-cognate tRNAs increase the efficiency and precision of pseudouridine-mediated readthrough of premature termination codons. Nat. Biotechnol. 43, 114–123 (2025).
Roundtree, I. A., Evans, M. E., Pan, T. & He, C. Dynamic RNA modifications in gene expression regulation. Cell 169, 1187–1200 (2017).
Tahmasebi, S., Khoutorsky, A., Mathews, M. B. & Sonenberg, N. Translation deregulation in human disease. Nat. Rev. Mol. Cell Biol. 19, 791–807 (2018).
Sun, H. X., Li, K., Liu, C. & Yi, C. Q. Regulation and functions of non-m6A mRNA modifications. Nat. Rev. Mol. Cell Biol. 24, 714–731 (2023).
Fu, X. D. Non-coding RNA: a new frontier in regulatory biology. Natl Sci. Rev. 1, 190–204 (2014).
Ha, M. & Kim, V. N. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 15, 509–524 (2014).
Xiang, J. S., Schafer, D. M., Rothamel, K. L. & Yeo, G. W. Decoding protein–RNA interactions using CLIP-based methodologies. Nat. Rev. Genet. 25, 879–895 (2024).
Bass, B. L. & Weintraub, H. An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 55, 1089–1098 (1988).
Wagner, R. W., Smith, J. E., Cooperman, B. S. & Nishikura, K. A double-stranded-RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian-cells and Xenopus eggs. Proc. Natl Acad. Sci. USA 86, 2647–2651 (1989).
Melcher, T. et al. A mammalian RNA editing enzyme. Nature 379, 460–464 (1996).
Salter, J. D., Bennett, R. P. & Smith, H. C. The APOBEC protein family: united by structure, divergent in function. Trends Biochem. Sci. 41, 578–594 (2016).
Pecori, R., Di Giorgio, S., Lorenzo, J. P. & Papavasiliou, F. N. Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination. Nat. Rev. Genet. 23, 505–518 (2022).
Wolf, J., Gerber, A. P. & Keller, W. tadA, an essential tRNA-specific adenosine deaminase from. EMBO J. 21, 3841–3851 (2002).
Losey, H. C., Ruthenburg, A. J. & Verdine, G. L. Crystal structure of tRNA adenosine deaminase TadA in complex with RNA. Nat. Struct. Mol. Biol. 13, 153–159 (2006).
Yang, L. H. et al. Engineering and optimising deaminase fusions for genome editing. Nat. Commun. 7, 13330 (2016).
Lam, D. K. et al. Improved cytosine base editors generated from TadA variants. Nat. Biotechnol. 41, 686–697 (2023).
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).
Lapinaite, A. et al. DNA capture by a CRISPR–Cas9-guided adenine base editor. Science 369, 566–571 (2020).
Rees, H. A., Wilson, C., Doman, J. L. & Liu, D. R. Analysis and minimization of cellular RNA editing by DNA adenine base editors. Sci. Adv. 5, eaax5717 (2019).
Li, J. A. et al. Structure-guided engineering of adenine base editor with minimized RNA off-targeting activity. Nat. Commun. 12, 2287 (2021).
Grunewald, J. et al. CRISPR DNA base editors with reduced RNA off-target and self-editing activities. Nat. Biotechnol. 37, 1041–1048 (2019).
Zhou, C. Y. et al. Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis. Nature 571, 275–278 (2019).
Jeong, Y. K. et al. Adenine base editor engineering reduces editing of bystander cytosines. Nat. Biotechnol. 39, 1426–1433 (2021).
Gaudelli, N. M. et al. Directed evolution of adenine base editors with increased activity and therapeutic application. Nat. Biotechnol. 38, 892–U899 (2020).
Mort, M., Ivanov, D., Cooper, D. N. & Chuzhanova, N. A. A meta-analysis of nonsense mutations causing human genetic disease. Hum. Mutat. 29, 1037–1047 (2008).
Stenson, P. D. et al. The Human Gene Mutation Database: 2008 update. Genome Med. 1, 13 (2009).
Bidou, L., Allamand, V., Rousset, J. P. & Namy, O. Sense from nonsense: therapies for premature stop codon diseases. Trends Mol. Med. 18, 679–688 (2012).
Bidou, L. et al. Premature stop codons involved in muscular dystrophies show a broad spectrum of readthrough efficiencies in response to gentamicin treatment. Gene Ther. 11, 619–627 (2004).
Martins-Dias, P. & Romao, L. Nonsense suppression therapies in human genetic diseases. Cell. Mol. Life Sci. 78, 4677–4701 (2021).
Welch, E. M. et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 447, 87–91 (2007).
Shi, N. et al. Restoration of dystrophin expression in mice by suppressing a nonsense mutation through the incorporation of unnatural amino acids. Nat. Biomed. Eng. 6, 195–206 (2022).
Lueck, J. D. et al. Engineered transfer RNAs for suppression of premature termination codons. Nat. Commun. 10, 822 (2019).
Albers, S. et al. Engineered tRNAs suppress nonsense mutations in cells and in vivo. Nature 618, 842–848 (2023).
Wang, J. M. et al. AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice. Nature 604, 343–348 (2022).
Wong, S. K., Sato, S. & Lazinski, D. W. Substrate recognition by ADAR1 and ADAR2. RNA 7, 846–858 (2001).
Matthews, M. M. et al. Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity. Nat. Struct. Mol. Biol. 23, 426–433 (2016).
Azad, M. T. A., Bhakta, S. & Tsukahara, T. Site-directed RNA editing by adenosine deaminase acting on RNA for correction of the genetic code in gene therapy. Gene Ther. 24, 779–786 (2017).
Dugueperoux, I. et al. Cystic fibrosis at the Reunion Island (France): spectrum of mutations and genotype–phenotype for the Y122X mutation. J. Cyst. Fibros. 3, 185–188 (2004).
Karijolich, J. & Yu, Y. T. Therapeutic suppression of premature termination codons: mechanisms and clinical considerations (review). Int. J. Mol. Med. 34, 355–362 (2014).
Neugebauer, M. E. et al. Evolution of an adenine base editor into a small, efficient cytosine base editor with low off-target activity. Nat. Biotechnol. 41, 673–685 (2023).
Chen, L. et al. Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing. Nat. Biotechnol. 41, 663–672 (2023).
Zhang, E., Neugebauer, M. E., Krasnow, N. A. & Liu, D. R. Phage-assisted evolution of highly active cytosine base editors with enhanced selectivity and minimal sequence context preference. Nat. Commun. 15, 1697 (2024).
Li, Z. Y. et al. dbPTM in 2022: an updated database for exploring regulatory networks and functional associations of protein post-translational modifications. Nucleic Acids Res. 50, D471–D479 (2022).
Rao, R. S. P. & Moller, I. M. Large-scale analysis of phosphorylation site occupancy in eukaryotic proteins. Biochim. Biophys. Acta 1824, 405–412 (2012).
Schweiger, R. & Linial, M. Cooperativity within proximal phosphorylation sites is revealed from large-scale proteomics data. Biol. Direct 5, 6 (2010).
Zheng, L. et al. Phosphorylation of stem-loop binding protein (SLBP) on two threonines triggers degradation of SLBP, the sole cell cycle-regulated factor required for regulation of histone mRNA processing, at the end of S phase. Mol. Cell. Biol. 23, 1590–1601 (2003).
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).
Yu, Y. et al. Cytosine base editors with minimized unguided DNA and RNA off-target events and high on-target activity. Nat. Commun. 11, 2052 (2020).
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).
Zhang, X. H. et al. Dual base editor catalyzes both cytosine and adenine base conversions in human cells. Nat. Biotechnol. 38, 856–U810 (2020).
Li, C. et al. Targeted, random mutagenesis of plant genes with dual cytosine and adenine base editors. Nat. Biotechnol. 38, 875–U866 (2020).
Grünewald, J. et al. A dual-deaminase CRISPR base editor enables concurrent adenine and cytosine editing. Nat. Biotechnol. 38, 861–U827 (2020).
Sakata, R. C. et al. Base editors for simultaneous introduction of C-to-T and A-to-G mutations. Nat. Biotechnol. 38, 865–U846 (2020).
Weber, L. et al. Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype. Sci. Adv. 6, eaay9392 (2020).
Antoniou, P. et al. Base-editing-mediated dissection of a γ-globin-regulatory element for the therapeutic reactivation of fetal hemoglobin expression. Nat. Commun. 13, 6618 (2022).
Lebek, S. et al. Ablation of CaMKIId oxidation by CRISPR–Cas9 base editing as a therapy for cardiac disease. Science 379, 179–185 (2023).
Yan, H. & Tang, W. Programmed RNA editing with an evolved bacterial adenosine deaminase. Nat. Chem. Biol. 20, 1361–1370 (2024).
Giudice, G., Sanchez-Cabo, F., Torroja, C. & Lara-Pezzi, E. ATtRACT—a database of RNA-binding proteins and associated motifs. Database (Oxf.) 2016, baw035 (2016).
Kluesner, M. G. et al. EditR: a method to quantify base editing from Sanger sequencing. CRISPR J. 1, 239–250 (2018).
Gibson, D. G. et al. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat. Methods 6, 343–345 (2009).
Engler, C., Kandzia, R. & Marillonnet, S. A one pot, one step, precision cloning method with high throughput capability. PLoS ONE 3, e3647 (2008).
Cheng, E. C. K., Lam, J. K. C. & Kwon, S. C. Cytosolic CRISPR RNAs for efficient application of RNA-targeting CRISPR–Cas systems. EMBO Rep. 26, 1891–1912 (2025).
Lu, B. et al. Transposase assisted tagmentation of RNA/DNA hybrid duplexes. Elife 9, e54919 (2020).
Lu, B. & Yi, C. TRACE-seq: rapid, low-input, one-tube RNA-seq library construction based on tagmentation of RNA/DNA hybrids. Curr. Protoc. 3, e735 (2023).
