2020
DOI: 10.1038/s41587-020-0592-2
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Glycosylase base editors enable C-to-A and C-to-G base changes

Abstract: A-to-G), but cannot produce base transversions. Here we present BEs that cause C-to-A transversions in E. coli and C-to-G transversions in mammalian cells. Our glycosylase base editors (GBEs) consist of a Cas9 nickase, a cytidine deaminase and a Uracil-DNA glycosylase (Ung). Ung excises the U base created by the deaminase, creating an apurinic/apyrimidinic (AP) site that initiates the DNA repair process. [AU: unclear how this results in a transversion. Can this be

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Cited by 353 publications
(236 citation statements)
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“…Some existing strategies could be used to expand the targeting scope of ACBE because previous studies have developed many variants of CRISPR-Cas protein requiring different PAM sequences or the restricted-less PAMs [31,32]. Recently, C-to-G base editors consisted of a Cas9 nickase, a cytidine deaminase variant, and uracil DNA N-glycosylase (eUNG), which could induce targeted C-to-G transversions with a high editing specificity in mammalian cells [33,34]. Similarly, new dual-function base editors could be generated to simultaneously induce C-to-G and A-to-G by using the strategies established in this study.…”
Section: Discussionmentioning
confidence: 99%
“…Some existing strategies could be used to expand the targeting scope of ACBE because previous studies have developed many variants of CRISPR-Cas protein requiring different PAM sequences or the restricted-less PAMs [31,32]. Recently, C-to-G base editors consisted of a Cas9 nickase, a cytidine deaminase variant, and uracil DNA N-glycosylase (eUNG), which could induce targeted C-to-G transversions with a high editing specificity in mammalian cells [33,34]. Similarly, new dual-function base editors could be generated to simultaneously induce C-to-G and A-to-G by using the strategies established in this study.…”
Section: Discussionmentioning
confidence: 99%
“…Recently, novel forms of DNA base editing such as a C>G editing [15][16][17] , and simultaneous C and A editing [18][19][20][21] have been suggested, which would substantially expand the utilities of DNA base editors. Along with the intense efforts to improve DNA base editors, our suggested tools, high-delity ABE variants that exhibit minimized cytosine catalysis and reduced off-target RNA editing, and TC-speci c base editors with negligible bystander effects, should make DNA base editing tools a more attractive alternative for gene editing in many research areas, such as disease therapy development, gene regulation, and plant transformation.…”
mentioning
confidence: 99%
“…By mutating the codons encoding amino acids to stop codons, the researchers successfully inactivated the corresponding genes in E. coli [18], C. glutamicum [85], Klebsiella pneumoniae [87], and Staphylococcus aureus [88], which proved that the CBE tool can achieve gene inactivation. At present, the ABE base editor is only used to realize A to G base changes in E. coli [84,89]. The biggest advantage of the base editor compared with CRISPR/Cas9-guided gene editing is that it does not cause bacterial death, but a major disadvantage is that it can only induce base replacement, leading to mutation or gene inactivation, and cannot be used for gene insertions or deletions.…”
Section: Crispr/dcas9-mediated Base Editormentioning
confidence: 99%