Journal Article

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

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

2019

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adenine / Agrobacterium - genetics / Animal models / Change detection / CRISPR / Cytosine / Deoxyribonucleic acid / DNA / DNA damage / DNA Mutational Analysis - methods / DNA repair / Editing / Embryos / Fidelity / Gene Editing - methods / Gene sequencing / Genetic modification / Genetics / Genome editing / Genomes / Heterogeneity / In vivo methods and tests / Medical treatment / Monitoring methods / Mutation / Oryza / Oryza - genetics / Oryza - microbiology / Polymorphism, Single Nucleotide / Proteins / Ribonucleic acid / Rice / RNA / Target detection / Target recognition / Whole genome sequencing / Whole Genome Sequencing - methods