Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor
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Dear Editor,Base editors (BEs) have been recently developed by combining the APOBEC (apolipoprotein B mRNA editing enzyme,catalytic polypeptide-like)/AID (activation-induced deaminase) cytidine deaminase family members ”1” with the CRISPR/Cas9 system to perform targeted C-to-T base editing ”2-8”.Mechanistically,Cas9 variant-fused APOBEC/AID is directed to target site by sgRNA,introducing C-to-T substitution at the single-base level ”2-4”.Compared to earlier generations of BEs (BE1 and BE2),the latest BE3 achieved much higher base editing frequencies by substituting catalytically-dead Cas9 (dCas9) with Cas9 nickase (nCas9) ”2”.
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We thank Drs Xingxu Huang;Haopeng Wang ShanghaiTech University for discussion of this work,and Ms Xiao Wang for participation in experiments.This work is supported by the National Natural Science Foundation of China31600619,31600654,31471241 and 91540115;the Ministry of Science and Technology of China2014CB910600;Shanghai Municipal Science and Technology Commission16PJ1407000 and 16PJ1407500