biostudies-literatureXie JScience and Technology Planning Project of Guangdong ProvinceResearch Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical SciencesScience and Technology Program of GuangzhouNational Key Research and Development Program of China Stem Cell and Translational ResearchNational Natural Science Foundation of ChinaKey Research &amp; Development Program of Guangzhou Regenerative Medicine and Health Guangdong LaboratoryYouth Innovation Promotion Association of the Chinese Academy of Sciences131https://www.ebi.ac.uk/biostudies/studies/S-EPMC7510086biostudies-literatureUnknown18(1)<h4>Background</h4>Many favorable traits of crops and livestock and human genetic diseases arise from multiple single nucleotide polymorphisms or multiple point mutations with heterogeneous base substitutions at the same locus. Current cytosine or adenine base editors can only accomplish C-to-T (G-to-A) or A-to-G (T-to-C) substitutions in the windows of target genomic sites of organisms; therefore, there is a need to develop base editors that can simultaneously achieve C-to-T and A-to-G substitutions at the targeting site.<h4>Results</h4>In this study, a novel fusion adenine and cytosine base editor (ACBE) was generated by fusing a heterodimer of TadA (ecTadA^WT/*) and an activation-induced cytidine deaminase (AID) to the N- and C-terminals of Cas9 nickase (nCas9), respectively. BMC biologyACBE, a new base editor for simultaneous C-to-T and A-to-G substitutions in mammalian systems.PMC7510086202002030382202007030003816723172017B0202310012017YFA01051032017B0303140562019-I2M-5-025201704030034817021158194100420193472018GZR110104004Jin QLiang YChen FQuan LYe YWang JZhang QZhuang ZWang KLi NZhao XWu HLian MGe WXie JHuang XWang XOuyang ZGou SLai LShi HfalseACBE, a new base editor for simultaneous C-to-T and A-to-G substitutions in mammalian systems.<h4>Background</h4>Many favorable traits of crops and livestock and human genetic diseases arise from multiple single nucleotide polymorphisms or multiple point mutations with heterogeneous base substitutions at the same locus. Current cytosine or adenine base editors can only accomplish C-to-T (G-to-A) or A-to-G (T-to-C) substitutions in the windows of target genomic sites of organisms; therefore, there is a need to develop base editors that can simultaneously achieve C-to-T and A-to-G substitutions at the targeting site.<h4>Results</h4>In this study, a novel fusion adenine and cytosine base editor (ACBE) was generated by fusing a heterodimer of TadA (ecTadA^WT/*) and an activation-induced cytidine deaminase (AID) to the N- and C-terminals of Cas9 nickase (nCas9), respectively. 2020-01-01T00:00:00Z2020 Sep2025-04-04T22:04:15.824Z2020-09-30T07:04:15ZS-EPMC75100863296766410.1186/s12915-020-00866-5