TadA orthologs enable both cytosine and adenine editing of base editors.

Gene Editing Cytosine Adenine DNA RNA Adenosine / genetics CRISPR-Cas Systems / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 01 2023
Historique:
received: 19 08 2022
accepted: 09 01 2023
entrez: 26 1 2023
pubmed: 27 1 2023
medline: 31 1 2023
Statut: epublish

Résumé

Cytidine and adenosine deaminases are required for cytosine and adenine editing of base editors respectively, and no single deaminase could enable concurrent and comparable cytosine and adenine editing. Additionally, distinct properties of cytidine and adenosine deaminases lead to various types of off-target effects, including Cas9-indendepent DNA off-target effects for cytosine base editors (CBEs) and RNA off-target effects particularly severe for adenine base editors (ABEs). Here we demonstrate that 25 TadA orthologs could be engineered to generate functional ABEs, CBEs or ACBEs via single or double mutations, which display minimized Cas9-independent DNA off-target effects and genotoxicity, with orthologs B5ZCW4, Q57LE3, E8WVH3, Q13XZ4 and B3PCY2 as promising candidates for further engineering. Furthermore, RNA off-target effects of TadA ortholog-derived base editors could be further reduced or even eliminated by additional single mutation. Taken together, our work expands the base editing toolkits, and also provides important clues for the potential evolutionary process of deaminases.

Identifiants

DOI: 10.1038/s41467-023-36003-3 PMID: 36702837 PMC: PMC9880001
pubmed: 36702837
doi: 10.1038/s41467-023-36003-3
pii: 10.1038/s41467-023-36003-3
pmc: PMC9880001
doi:

Substances chimiques

Cytosine 8J337D1HZY
Adenine JAC85A2161
DNA 9007-49-2
RNA 63231-63-0
Adenosine K72T3FS567

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

414

Informations de copyright

© 2023. The Author(s).

Références

Nat Commun. 2020 Nov 17;11(1):5827
pubmed: 33203850
Cell. 2020 Jul 23;182(2):463-480.e30
pubmed: 32533916
Nat Methods. 2016 Dec;13(12):1029-1035
pubmed: 27723754
Nature. 2019 May;569(7756):433-437
pubmed: 30995674
Nat Biotechnol. 2020 Jul;38(7):856-860
pubmed: 32483363
Nat Biotechnol. 2020 Jul;38(7):892-900
pubmed: 32284586
Nat Commun. 2020 Sep 25;11(1):4871
pubmed: 32978399
Nat Struct Mol Biol. 2007 Jan;14(1):7-9
pubmed: 17203067
Nat Commun. 2019 Aug 9;10(1):3612
pubmed: 31399578
Nat Biotechnol. 2020 May;38(5):620-628
pubmed: 32042165
Nat Commun. 2020 Apr 28;11(1):2052
pubmed: 32345976
Nat Methods. 2016 Dec;13(12):1036-1042
pubmed: 27798611
Nat Commun. 2021 Apr 16;12(1):2287
pubmed: 33863894
Nat Biotechnol. 2019 Sep;37(9):1041-1048
pubmed: 31477922
Nat Biotechnol. 2018 Oct;36(9):843-846
pubmed: 29813047
Nat Biotechnol. 2022 Nov 10;:
pubmed: 36357717
Nat Biotechnol. 2020 Sep;38(9):1037-1043
pubmed: 32632303
Sci Adv. 2019 May 08;5(5):eaax5717
pubmed: 31086823
Nature. 2017 Nov 23;551(7681):464-471
pubmed: 29160308
Nat Biotechnol. 2022 Nov 10;:
pubmed: 36357719
BMC Biol. 2020 Sep 23;18(1):131
pubmed: 32967664
Nat Commun. 2020 Nov 27;11(1):6073
pubmed: 33247095
Nat Biotechnol. 2020 Jul;38(7):861-864
pubmed: 32483364
Science. 1999 Nov 5;286(5442):1146-9
pubmed: 10550050
Mol Biol Evol. 2018 Aug 1;35(8):2046-2059
pubmed: 29846694
Nat Biotechnol. 2018 Nov;36(10):977-982
pubmed: 30059493
Nat Biotechnol. 2020 Jul;38(7):883-891
pubmed: 32433547
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nature. 2016 Apr 20;533(7603):420-4
pubmed: 27096365
Science. 2016 Sep 16;353(6305):
pubmed: 27492474
Nat Methods. 2020 Jun;17(6):600-604
pubmed: 32424272
Proc Natl Acad Sci U S A. 2007 May 8;104(19):7821-6
pubmed: 17483465
Nat Rev Genet. 2022 Aug;23(8):505-518
pubmed: 35256818
Cell Rep. 2020 Jun 2;31(9):107723
pubmed: 32492431
Nat Biotechnol. 2019 Jun;37(6):626-631
pubmed: 31110355
Science. 2019 Apr 19;364(6437):292-295
pubmed: 30819931
Nat Chem Biol. 2021 Dec;17(12):1262-1270
pubmed: 34663942
Nat Biotechnol. 2019 Oct;37(10):1145-1148
pubmed: 31548727
Nature. 2019 Jul;571(7764):275-278
pubmed: 31181567
Nat Biotechnol. 2021 Nov;39(11):1426-1433
pubmed: 34211162
Science. 2019 Apr 19;364(6437):289-292
pubmed: 30819928

Auteurs

Shuqian Zhang (S)

Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.
Department of Pediatrics, Qilu Hospital of Shandong University, Ji'nan, 250012, China.

Bo Yuan (B)

Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
ORCID: 0000-0001-6382-1269

Jixin Cao (J)

Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.

Liting Song (L)

Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.

Jinlong Chen (J)

Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.

Jiayi Qiu (J)

Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.

Zilong Qiu (Z)

Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
National Clinical Research Center for Aging and Medicine, Huashan Hopsital, Fudan University, Shanghai, 200032, China.
Songjiang Hospital, Songjiang Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
ORCID: 0000-0003-4286-3288

Xing-Ming Zhao (XM)

Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, China.
MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
ORCID: 0000-0002-4531-3970

Jingqi Chen (J)

Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, China.
MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
ORCID: 0000-0002-2454-0058

Tian-Lin Cheng (TL)

Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China. chengtianlin@fudan.edu.cn.
ORCID: 0000-0003-0680-6710

Articles similaires

Generation of isogenic models of Angelman syndrome and Prader-Willi syndrome in CRISPR/Cas9-engineered human embryonic stem cells.

Rachel B Gilmore, Dea Gorka, Christopher E Stoddard et al.
1.00
Prader-Willi Syndrome Humans Angelman Syndrome CRISPR-Cas Systems Human Embryonic Stem Cells

Biological functions and molecular mechanisms of exosome-derived circular RNAs and their clinical implications in digestive malignancies: the vintage in the bottle.

Yuanyan Lou, Jianing Yan, Qingqing Liu et al.
1.00
Humans RNA, Circular Exosomes Cell Proliferation Epithelial-Mesenchymal Transition

iDNA-ITLM: An interpretable and transferable learning model for identifying DNA methylation.

Xia Yu, Cui Yani, Zhichao Wang et al.
1.00
DNA Methylation Humans DNA Animals Machine Learning

Structural basis for human OGG1 processing 8-oxodGuo within nucleosome core particles.

Mengtian Ren, Fabian Gut, Yilan Fan et al.
1.00
DNA Glycosylases Nucleosomes Humans 8-Hydroxy-2'-Deoxyguanosine DNA Repair

Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Édition de gène › TadA orthologs enable both cytosine and...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › Pyrimidinones › Cytosine › TadA orthologs enable both cytosine and...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › Adénine › TadA orthologs enable both cytosine and...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › TadA orthologs enable both cytosine and...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › TadA orthologs enable both cytosine and...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Ribonucléosides › Adénosine › TadA orthologs enable both cytosine and...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Systèmes CRISPR-Cas › TadA orthologs enable both cytosine and...