Nucleoside Deaminases: the Key Players in Base Editing Toolkit

Overview

Journal Biophys Rep

Specialty Biochemistry

Date 2024 Mar 25

PMID 38524700

Authors

Jiangchao Xiang

Wenchao Xu

Jing Wu

Yaxin Luo

Bei Yang

Jia Chen

Affiliations

Soon will be listed here.

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.

References

Losey H, Ruthenburg A, Verdine G . Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNA. Nat Struct Mol Biol. 2006; 13(2):153-9. DOI: 10.1038/nsmb1047. View

Doudna J . The promise and challenge of therapeutic genome editing. Nature. 2020; 578(7794):229-236. PMC: 8992613. DOI: 10.1038/s41586-020-1978-5. View

Reautschnig P, Wahn N, Wettengel J, Schulz A, Latifi N, Vogel P . CLUSTER guide RNAs enable precise and efficient RNA editing with endogenous ADAR enzymes in vivo. Nat Biotechnol. 2022; 40(5):759-768. DOI: 10.1038/s41587-021-01105-0. View

Huang T, Newby G, Liu D . Precision genome editing using cytosine and adenine base editors in mammalian cells. Nat Protoc. 2021; 16(2):1089-1128. DOI: 10.1038/s41596-020-00450-9. View

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

Katrekar D, Yen J, Xiang Y, Saha A, Meluzzi D, Savva Y . Efficient in vitro and in vivo RNA editing via recruitment of endogenous ADARs using circular guide RNAs. Nat Biotechnol. 2022; 40(6):938-945. PMC: 9232839. DOI: 10.1038/s41587-021-01171-4. View

Wang L, Xue W, Zhang H, Gao R, Qiu H, Wei J . Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations. Nat Cell Biol. 2021; 23(5):552-563. DOI: 10.1038/s41556-021-00671-4. View

Abudayyeh O, Gootenberg J, Franklin B, Koob J, Kellner M, Ladha A . A cytosine deaminase for programmable single-base RNA editing. Science. 2019; 365(6451):382-386. PMC: 6956565. DOI: 10.1126/science.aax7063. View

Yang B, Yang L, Chen J . Development and Application of Base Editors. CRISPR J. 2019; 2(2):91-104. DOI: 10.1089/crispr.2019.0001. View

10.

Qu L, Yi Z, Zhu S, Wang C, Cao Z, Zhou Z . Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs. Nat Biotechnol. 2019; 37(9):1059-1069. DOI: 10.1038/s41587-019-0178-z. View

11.

Goodman R, Macbeth M, Beal P . ADAR proteins: structure and catalytic mechanism. Curr Top Microbiol Immunol. 2011; 353:1-33. DOI: 10.1007/82_2011_144. View

12.

Yang L, Chen J . A Tale of Two Moieties: Rapidly Evolving CRISPR/Cas-Based Genome Editing. Trends Biochem Sci. 2020; 45(10):874-888. DOI: 10.1016/j.tibs.2020.06.003. View

13.

Zheng Y, Lorenzo C, Beal P . DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA. Nucleic Acids Res. 2017; 45(6):3369-3377. PMC: 5389660. DOI: 10.1093/nar/gkx050. View

14.

Huang X, Lv J, Li Y, Mao S, Li Z, Jing Z . Programmable C-to-U RNA editing using the human APOBEC3A deaminase. EMBO J. 2021; 40(9):e108209. PMC: 8090828. DOI: 10.15252/embj.2021108209. View

15.

Mok B, de Moraes M, Zeng J, Bosch D, Kotrys A, Raguram A . A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature. 2020; 583(7817):631-637. PMC: 7381381. DOI: 10.1038/s41586-020-2477-4. View

16.

Wolf J, Gerber A, Keller W . tadA, an essential tRNA-specific adenosine deaminase from Escherichia coli. EMBO J. 2002; 21(14):3841-51. PMC: 126108. DOI: 10.1093/emboj/cdf362. View

17.

Doman J, Raguram A, Newby G, Liu D . Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors. Nat Biotechnol. 2020; 38(5):620-628. PMC: 7335424. DOI: 10.1038/s41587-020-0414-6. View

18.

Komor A, Kim Y, Packer M, Zuris J, Liu D . Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016; 533(7603):420-4. PMC: 4873371. DOI: 10.1038/nature17946. View

19.

Yi Z, Qu L, Tang H, Liu Z, Liu Y, Tian F . Engineered circular ADAR-recruiting RNAs increase the efficiency and fidelity of RNA editing in vitro and in vivo. Nat Biotechnol. 2022; 40(6):946-955. DOI: 10.1038/s41587-021-01180-3. View

20.

Salter J, Smith H . Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands. Trends Biochem Sci. 2018; 43(8):606-622. PMC: 6073885. DOI: 10.1016/j.tibs.2018.04.013. View