Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice
Top Cited Papers
- 19 April 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 364 (6437), 292-295
- https://doi.org/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.Keywords
Funding Information
- National Natural Science Foundation of China (31788103)
- Chinese Academy of Sciences (QYZDY-SSW-SMC030)
- National Key Research and Development Program of China (2016YFD0101804)
- college of biological sciences, University of Minnesota startup funding
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