SsCBE是通过将SsdAtox融合到nCas9(Cas9的突变体,失去核酸酶活性但保留DNA结合能力)上构建的。为了提高编辑效率和减少脱靶效应,SsCBE还融合了尿嘧啶-DNA糖基化酶抑制剂(UGI)域。同时对SsdAtox进行了关键氨基酸突变,包括P282S、Y335R和K392E,形成了SRE(Specificity and Reduced toxicity)变体,显著提高了编辑效率和减少了细胞毒性。
Kweon, J. et al. High-efficiency base editing for nuclear and mitochondrial DNA with an optimized DYW-like deaminase. Mol. Ther. J. Am. Soc. Gene Ther. S1525-0016(25)00637–9 (2025) doi:10.1016/j.ymthe.2025.08.007.