Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice.
Authors: Jin Shuai, Zong Yuan, Gao Qiang, Zhu Zixu, Wang Yanpeng, Qin Peng, Liang Chengzhi, Wang Daowen, Qiu Jin-Long, Zhang Feng, Gao Caixia
Journal: Science (New York, N.Y.) (Science), Vol.364(6437), 2019‑Apr‑19
DOI:
10.1126/science.aaw7166
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.
Publication Types
Journal Article
Research Support, Non-U.S. Gov't
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