Current base-editing techniques can only facilitate C-to-T editing and A-to-G editing, so a complete base-editing technique for converting any base to any other base is highly desirable.
On July 20, 2020, Dr. Changhao Bi’s team and Dr. Xueli Zhang’s team at Tianjin Institute of Industrial Biotechnology published a paper "Glycosylase base editors enable C-to-A and C-to-G base changes”. They present BEs that cause C-to-A transversions in Escherichia coli and C-to-G transversions in mammalian cells.
These 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, forming an apurinic/apyrimidinic (AP) site that initiates the DNA repair process. In E. coli, they used activation-induced cytidine deaminase (AID) to construct AID-nCas9-Ung and found that it converts C to A with an average editing specificity of 93.8% ± 4.8% and editing efficiency of 87.2% ± 6.9%. For use in mammalian cells, they replaced AID with rat APOBEC1 (APOBEC-nCas9-Ung). They tested APOBEC-nCas9-Ung at 30 endogenous sites, and they observed C-to-G conversions with a high editing specificity at the sixth position of the protospacer between 29.7% and 92.2% and an editing efficiency between 5.3% and 53.0%. APOBEC-nCas9-Ung supplements the current adenine and cytidine BEs (ABE and CBE, respectively) and could be used to target G/C disease-causing mutations.
Fig. 1: Base editing in E. coli using nCas9-AID and Ung-nCas9-AID fusion.
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