Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice
Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice
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DOI：
10.1126/science.aaw7166
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发表时间：
2019-04-19
期刊：
影响因子：
56.9
通讯作者：
Gao, Caixia
中科院分区：
文献类型：
--
作者：
Jin, Shuai;Zong, Yuan;Gao, Caixia
胞嘧啶和腺嘌呤碱基编辑器（CBE和ABE）是实现疾病治疗和性状改良所需的精确遗传变化的有前途的新工具。然而，仍然缺乏对其体内脱靶效应的全基因组和无偏倚分析。我们对用第三代碱基编辑器（BE 3）、高保真BE 3（HF 1-BE 3）或ABE处理的水稻植物进行的全基因组测序分析显示，BE 3和HF 1-BE 3，而不是ABE，诱导了大量的全基因组脱靶突变，这些突变主要是C -> T类型的单核苷酸变体（SNV），并且似乎在基因区域中富集。值得注意的是，在不存在单向导RNA的情况下用BE 3或HF 1-BE 3处理水稻也导致全基因组SNV的增加。因此，需要优化BE 3或HF 1-BE 3的碱基编辑单元以获得高保真度。
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.