Nucleoside deaminases: the key players in base editing toolkit

Jiangchao Xiang; Wenchao Xu; Jing Wu; Yaxin Luo; Bei Yang; Jia Chen

doi:10.52601/bpr.2023.230029

Volume 9 Issue 6

Dec. 2023

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Article Navigation > Biophysics Reports > 2023 > 9(6): 325-337

Jiangchao Xiang, Wenchao Xu, Jing Wu, Yaxin Luo, Bei Yang, Jia Chen. Nucleoside deaminases: the key players in base editing toolkit[J]. Biophysics Reports, 2023, 9(6): 325-337. doi: 10.52601/bpr.2023.230029

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Jiangchao Xiang, Wenchao Xu, Jing Wu, Yaxin Luo, Bei Yang, Jia Chen. Nucleoside deaminases: the key players in base editing toolkit[J]. Biophysics Reports, 2023, 9(6): 325-337. doi: 10.52601/bpr.2023.230029

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Nucleoside deaminases: the key players in base editing toolkit

doi: 10.52601/bpr.2023.230029

Jiangchao Xiang^{1, J},
Wenchao Xu^{1, J},
Jing Wu^{1, J},
Yaxin Luo²,
Bei Yang^{1, 2, 3
,
,},
Jia Chen^{1, 3
,
,}

1.
Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
2.
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China
3.
Shanghai Clinical Research and Trial Center, Shanghai 201210, China

More Information

Corresponding author: yangbei@shanghaitech.edu.cn (Bei Yang); chenjia@shanghaitech.edu.cn (Jia Chen)
Received Date: 30 October 2023
Accepted Date: 28 November 2023

Available Online: 26 February 2024

Publish Date: 31 December 2023

Abstract

Abstract

The development of nucleoside deaminase-containing base editors realized targeted single base change with high efficiency and precision. Such nucleoside deaminases include adenosine and cytidine deaminases, which can catalyze adenosine-to-inosine (A-to-I) and cytidine-to-uridine (C-to-U) conversion respectively. These nucleoside deaminases are under the spotlight because of their vast application potential in gene editing. Recent advances in the engineering of current nucleoside deaminases and the discovery of new nucleoside deaminases greatly broaden the application scope and improve the editing specificity of base editors. In this review, we cover current knowledge about the deaminases used in base editors, including their key structural features, working mechanisms, optimization, and evolution.
- Nucleoside deaminase,
- Base editors

Jiangchao Xiang, Wenchao Xu, Jing Wu, Yaxin Luo, Bei Yang and Jia Chen declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
Jiangchao Xiang, Wenchao Xu and Jing Wu contribute equally to this work.

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References(60)

References

Abudayyeh OO, Gootenberg JS, Franklin B, Koob J, Kellner MJ, Ladha A, Joung J, Kirchgatterer P, Cox DBT, Zhang F (2019) A cytosine deaminase for programmable single-base RNA editing. Science 365(6451): 382−386 doi: 10.1126/science.aax7063

Barrera-Paez JD, Moraes CT (2022) Mitochondrial genome engineering coming-of-age. Trends Genet 38(8): 869−880 doi: 10.1016/j.tig.2022.04.011

Bass BL, Nishikura K, Keller W, Seeburg PH, Emeson RB, O'Connell MA, Samuel CE, Herbert A (1997) A standardized nomenclature for adenosine deaminases that act on RNA. RNA 3(9): 947−949

Bass BL, Weintraub H (1988) An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 55(6): 1089−1098 doi: 10.1016/0092-8674(88)90253-X

Chen L, Zhang S, Xue N, Hong M, Zhang X, Zhang D, Yang J, Bai S, Huang Y, Meng H, Wu H, Luan C, Zhu B, Ru G, Gao H, Zhong L, Liu M, Liu M, Cheng Y, Yi C, Wang L, Zhao Y, Song G, Li D (2023) Engineering a precise adenine base editor with minimal bystander editing. Nat Chem Biol 19(1): 101−110 doi: 10.1038/s41589-022-01163-8

Cheng K, Li C, Jin J, Qian X, Guo J, Shen L, Dai Y, Zhang X, Li Z, Guan Y, Zhou F, Tang J, Zhang J, Shen B, Lou X (2023) Engineering RsDddA as mitochondrial base editor with wide target compatibility and enhanced activity. Mol Ther Nucleic Acids 34: 102028. https://doi.org/10.1016/j.omtn.2023.09.005

Cho SI, Lee S, Mok YG, Lim K, Lee J, Lee JM, Chung E, Kim JS (2022) Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases. Cell 185(10): 1764-1776 e1712

Cox DBT, Gootenberg JS, Abudayyeh OO, Franklin B, Kellner MJ, Joung J, Zhang F (2017) RNA editing with CRISPR-Cas13. Science 358(6366): 1019−1027 doi: 10.1126/science.aaq0180

Doman JL, Raguram A, Newby GA, Liu DR (2020) Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors. Nat Biotechnol 38(5): 620−628 doi: 10.1038/s41587-020-0414-6

Doudna JA (2020) The promise and challenge of therapeutic genome editing. Nature 578(7794): 229−236 doi: 10.1038/s41586-020-1978-5

Doudna JA, Charpentier E (2014) Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346(6213): 1258096. doi: 10.1126/science.1258096

Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, Liu DR (2017) Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551(7681): 464−471 doi: 10.1038/nature24644

Gehrke JM, Cervantes O, Clement MK, Wu Y, Zeng J, Bauer DE, Pinello L, Joung JK (2018) An APOBEC3A-Cas9 base editor with minimized bystander and off-target activities. Nat Biotechnol 36(10): 977−982 doi: 10.1038/nbt.4199

Goodman RA, Macbeth MR, Beal PA (2012) ADAR proteins: structure and catalytic mechanism. Curr Top Microbiol Immunol 353: 1−33

Grunewald J, Zhou R, Garcia SP, Iyer S, Lareau CA, Aryee MJ, Joung JK (2019a) Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569(7756): 433−437 doi: 10.1038/s41586-019-1161-z

Grunewald J, Zhou R, Iyer S, Lareau CA, Garcia SP, Aryee MJ, Joung JK (2019b) CRISPR DNA base editors with reduced RNA off-target and self-editing activities. Nat Biotechnol 37(9): 1041−1048 doi: 10.1038/s41587-019-0236-6

Guo J, Yu W, Li M, Chen H, Liu J, Xue X, Lin J, Huang S, Shu W, Huang X, Liu Z, Wang S, Qiao Y (2023) A DddA ortholog-based and transactivator-assisted nuclear and mitochondrial cytosine base editors with expanded target compatibility. Mol Cell 83(10): 1710-1724 e1717

Hess GT, Fresard L, Han K, Lee CH, Li A, Cimprich KA, Montgomery SB, Bassik MC (2016) Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells. Nat Methods 13(12): 1036−1042 doi: 10.1038/nmeth.4038

Huang J, Lin Q, Fei H, He Z, Xu H, Li Y, Qu K, Han P, Gao Q, Li B, Liu G, Zhang L, Hu J, Zhang R, Zuo E, Luo Y, Ran Y, Qiu JL, Zhao KT, Gao C (2023) Discovery of deaminase functions by structure-based protein clustering. Cell 186(15): 3182−3195.e14 doi: 10.1016/j.cell.2023.05.041

Huang TP, Newby GA, Liu DR (2021a) Precision genome editing using cytosine and adenine base editors in mammalian cells. Nat Protoc 16(2): 1089−1128 doi: 10.1038/s41596-020-00450-9

Huang X, Lv J, Li Y, Mao S, Li Z, Jing Z, Sun Y, Zhang X, Shen S, Wang X, Di M, Ge J, Huang X, Zuo E, Chi T (2021b) Programmable C-to-U RNA editing using the human APOBEC3A deaminase. EMBO J 40(9): e108209. https://doi.org/10.15252/embj.2021108209

Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096): 816−821 doi: 10.1126/science.1225829

Katrekar D, Yen J, Xiang Y, Saha A, Meluzzi D, Savva Y, Mali P (2022) Efficient in vitro and in vivo RNA editing via recruitment of endogenous ADARs using circular guide RNAs. Nat Biotechnol 40(6): 938−945 doi: 10.1038/s41587-021-01171-4

Kim J, Malashkevich V, Roday S, Lisbin M, Schramm VL, Almo SC (2006) Structural and kinetic characterization of Escherichia coli TadA, the wobble-specific tRNA deaminase. Biochemistry 45(20): 6407−6416 doi: 10.1021/bi0522394

Kim JS, Chen J (2023) Base editing of organellar DNA with programmable deaminases. Nat Rev Mol Cell Biol. doi:10.1038/s41580-023-00663-2. Online ahead of print

Kim YB, Komor AC, Levy JM, Packer MS, Zhao KT, Liu DR (2017) Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions. Nat Biotechnol 35(4): 371−376 doi: 10.1038/nbt.3803

Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533(7603): 420−424 doi: 10.1038/nature17946

Korf BR, Pyeritz RE, Grody WW (2019) 3-Nature and frequency of genetic disease. Pyeritz RE, Korf BR, Grody WW et al. (Eds). Academic Press. pp 47-51

Lapinaite A, Knott GJ, Palumbo CM, Lin-Shiao E, Richter MF, Zhao KT, Beal PA, Liu DR, Doudna JA (2020) DNA capture by a CRISPR-Cas9-guided adenine base editor. Science 369(6503): 566−571 doi: 10.1126/science.abb1390

Lee S, Lee H, Baek G, Kim JS (2023) Precision mitochondrial DNA editing with high-fidelity DddA-derived base editors. Nat Biotechnol 41(3): 378−386 doi: 10.1038/s41587-022-01486-w

Liu Z, Chen S, Shan H, Jia Y, Chen M, Song Y, Lai L, Li Z (2020) Precise base editing with CC context-specificity using engineered human APOBEC3G-nCas9 fusions. BMC Biol 18(1): 111. https://doi.org/10.1186/s12915-020-00849-6

Losey HC, Ruthenburg AJ, Verdine GL (2006) Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNA. Nat Struct Mol Biol 13(2): 153−159 doi: 10.1038/nsmb1047

Ma Y, Zhang J, Yin W, Zhang Z, Song Y, Chang X (2016) Targeted AID-mediated mutagenesis (TAM) enables efficient genomic diversification in mammalian cells. Nat Methods 13(12): 1029−1035 doi: 10.1038/nmeth.4027

Mali P, Esvelt KM, Church GM (2013) Cas9 as a versatile tool for engineering biology. Nat Methods 10(10): 957−963 doi: 10.1038/nmeth.2649

Merkle T, Merz S, Reautschnig P, Blaha A, Li Q, Vogel P, Wettengel J, Li JB, Stafforst T (2019) Precise RNA editing by recruiting endogenous ADARs with antisense oligonucleotides. Nat Biotechnol 37(2): 133−138 doi: 10.1038/s41587-019-0013-6

Mi L, Shi M, Li YX, Xie G, Rao X, Wu D, Cheng A, Niu M, Xu F, Yu Y, Gao N, Wei W, Wang X, Wang Y (2023) DddA homolog search and engineering expand sequence compatibility of mitochondrial base editing. Nat Commun 14(1): 874. https://doi.org/10.1038/s41467-023-36600-2

Mok BY, de Moraes MH, Zeng J, Bosch DE, Kotrys AV, Raguram A, Hsu F, Radey MC, Peterson SB, Mootha VK, Mougous JD, Liu DR (2020) A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature 583(7817): 631−637 doi: 10.1038/s41586-020-2477-4

Mok BY, Kotrys AV, Raguram A, Huang TP, Mootha VK, Liu DR (2022) CRISPR-free base editors with enhanced activity and expanded targeting scope in mitochondrial and nuclear DNA. Nat Biotechnol 40(9): 1378−1387 doi: 10.1038/s41587-022-01256-8

Nishida K, Arazoe T, Yachie N, Banno S, Kakimoto M, Tabata M, Mochizuki M, Miyabe A, Araki M, Hara KY, Shimatani Z, Kondo A (2016) Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science 353(6305): aaf8729. https://doi.org/10.1126/science.aaf8729

Pecori R, Di Giorgio S, Paulo Lorenzo J, Nina Papavasiliou F (2022) Functions and consequences of AID/APOBEC-mediated DNA and RNA deamination. Nat Rev Genet 23(8): 505−518 doi: 10.1038/s41576-022-00459-8

Qu L, Yi Z, Zhu S, Wang C, Cao Z, Zhou Z, Yuan P, Yu Y, Tian F, Liu Z, Bao Y, Zhao Y, Wei W (2019) Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs. Nat Biotechnol 37(9): 1059−1069 doi: 10.1038/s41587-019-0178-z

Reautschnig P, Wahn N, Wettengel J, Schulz AE, Latifi N, Vogel P, Kang TW, Pfeiffer LS, Zarges C, Naumann U, Zender L, Li JB, Stafforst T (2022) CLUSTER guide RNAs enable precise and efficient RNA editing with endogenous ADAR enzymes in vivo. Nat Biotechnol 40(5): 759−768 doi: 10.1038/s41587-021-01105-0

Rees HA, Wilson C, Doman JL, Liu DR (2019) Analysis and minimization of cellular RNA editing by DNA adenine base editors. Sci Adv 5(5): eaax5717. https://doi.org/10.1126/sciadv.aax5717

Richter MF, Zhao KT, Eton E, Lapinaite A, Newby GA, Thuronyi BW, Wilson C, Koblan LW, Zeng J, Bauer DE, Doudna JA, Liu DR (2020) Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat Biotechnol 38(7): 883−891 doi: 10.1038/s41587-020-0453-z

Salter JD, Bennett RP, Smith HC (2016) The APOBEC protein family: united by structure, divergent in function. Trends Biochem Sci 41(7): 578−594 doi: 10.1016/j.tibs.2016.05.001

Salter JD, Smith HC (2018) Modeling the embrace of a mutator: APOBEC selection of nucleic acid ligands. Trends Biochem Sci 43(8): 606−622 doi: 10.1016/j.tibs.2018.04.013

Savva YA, Rieder LE, Reenan RA (2012) The ADAR protein family. Genome Biol 13(12): 252. https://doi.org/10.1186/gb-2012-13-12-252

Wang JY, Doudna JA (2023) CRISPR technology: a decade of genome editing is only the beginning. Science 379(6629): eadd8643. https://doi.org/10.1126/science.add8643

Wang L, Xue W, Yan L, Li X, Wei J, Chen M, Wu J, Yang B, Yang L, Chen J (2017) Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor. Cell Res 27(10): 1289−1292 doi: 10.1038/cr.2017.111

Wang L, Xue W, Zhang H, Gao R, Qiu H, Wei J, Zhou L, Lei YN, Wu X, Li X, Liu C, Wu J, Chen Q, Ma H, Huang X, Cai C, Zhang Y, Yang B, Yin H, Yang L, Chen J (2021) Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations. Nat Cell Biol 23(5): 552−563 doi: 10.1038/s41556-021-00671-4

Wang X, Ding C, Yu W, Wang Y, He S, Yang B, Xiong YC, Wei J, Li J, Liang J, Lu Z, Zhu W, Wu J, Zhou Z, Huang X, Liu Z, Yang L, Chen J (2020) Cas12a base editors induce efficient and specific editing with low DNA damage response. Cell Rep 31(9): 107723. https://doi.org/10.1016/j.celrep.2020.107723

Wang X, Li J, Wang Y, Yang B, Wei J, Wu J, Wang R, Huang X, Chen J, Yang L (2018) Efficient base editing in methylated regions with a human APOBEC3A-Cas9 fusion. Nat Biotechnol 36(10): 946−949 doi: 10.1038/nbt.4198

Wedekind JE, Dance GS, Sowden MP, Smith HC (2003) Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business. Trends Genet 19(4): 207−216 doi: 10.1016/S0168-9525(03)00054-4

Wolf J, Gerber AP, Keller W (2002) tadA, an essential tRNA-specific adenosine deaminase from Escherichia coli. EMBO J 21(14): 3841−3851 doi: 10.1093/emboj/cdf362

Yang B, Li X, Lei L, Chen J (2017) APOBEC: from mutator to editor. J Genet Genomics 44(9): 423−437 doi: 10.1016/j.jgg.2017.04.009

Yang B, Yang L, Chen J (2019) Development and application of base editors. CRISPR J 2(2): 91−104 doi: 10.1089/crispr.2019.0001

Yang L, Chen J (2020) A Tale of Two Moieties: rapidly evolving CRISPR/Cas-based genome editing. Trends Biochem Sci 45(10): 874−888 doi: 10.1016/j.tibs.2020.06.003

Yi Z, Qu L, Tang H, Liu Z, Liu Y, Tian F, Wang C, Zhang X, Feng Z, Yu Y, Yuan P, Yi Z, Zhao Y, Wei W (2022) Engineered circular ADAR-recruiting RNAs increase the efficiency and fidelity of RNA editing in vitro and in vivo. Nat Biotechnol 40(6): 946−955 doi: 10.1038/s41587-021-01180-3

Zheng Y, Lorenzo C, Beal PA (2017) DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA. Nucleic Acids Res 45(6): 3369−3377

Zhou C, Sun Y, Yan R, Liu Y, Zuo E, Gu C, Han L, Wei Y, Hu X, Zeng R, Li Y, Zhou H, Guo F, Yang H (2019) Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis. Nature 571(7764): 275−278 doi: 10.1038/s41586-019-1314-0

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