Cytosine base editors (CBEs) can convert cytosines (C) to thymines (T), which is composed by fusing a deaminase with the Cas9 nickase (nCas9). CBEs are designed to reverse T-to-C mutations in human genome which attribute to about 38% of human pathogenic diseases. However, CBEs could introduce unwanted bystander editing, resulting in unwanted C-to-T conversions when there exists a continuous sequence of C.
This July, Erwei Zuo’s group from Chinese Academy of Agricultural Sciences collaborate with Xue Gao’s research lab from Rice University has published a new model of CBE called A3G-BEs. A3G-BEs has dramatically increased precision when editing the second C of consecutive Cs avoiding bystander C. In their experiments, A3G-BEs performed with an over 6,000-fold higher correction compared to the current "state-of-art"CBE, BE4max, on pathogenetic mutations in cell models.
Not only the precision of base editing has enhanced in A3G-BEs but also decrease of off-target edits has been shown in A3G-BEs. Gao believes that A3G-BEs is going to be a significant contributor toward treating genetic disease and increasing CBEs precision will be the trend in CBE engineer.
Sangsin Lee et al. Single C-to-T substitution using engineered APOBEC3G-nCas9 base editors with minimum genome- and transcriptome-wide off-target effects.Science Advances, 2020, doi:10.1126/sciadv.aba1773.