Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice 

Shuai Jin#,Yuan Zong#, Qiang Gao#, Zixu Zhu,Yanpeng Wang, Peng Qin, Chengzhi Liang, Daowen Wang, Jin-Long Qiu, Feng Zhang, Caixia Gao*

Science（IF=41.058），2019，36（6437）：292-295

https://science.sciencemag.org/content/364/6437/292.full

Abstract

Cytosine and adenine base editors (CBEs and ABEs) are promising new tools for achieving the precise genetic changes required for disease treatment and trait improvement. However, genome-wide and unbiased analyses of their off-target effects in vivo are still lacking. Our whole-genome sequencing analysis of rice plants treated with the third-generation base editor (BE3), high-fidelity BE3 (HF1-BE3), or ABE revealed that BE3 and HF1-BE3, but not ABE, induce substantial genome-wide off-target mutations, which are mostly the C→T type of single-nucleotide variants (SNVs) and appear to be enriched in genic regions. Notably, treatment of rice with BE3 or HF1-BE3 in the absence of single-guide RNA also results in the rise of genome-wide SNVs. Thus, the base-editing unit of BE3 or HF1-BE3 needs to be optimized in order to attain high fidelity.