|
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
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 (WGS) analysis of rice plants treated with 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.
|
论文编号: |
DOI:10.1126/science.aaw7166 |
论文题目: |
Cytosine, But not Adenine, Base Editors Induce Genome-wide Off-target Mutations in Rice |
英文论文题目: |
Cytosine, But not Adenine, Base Editors Induce Genome-wide Off-target Mutations in Rice |
第一作者: |
Shuai Jin, Yuan Zong, Qiang Gao, Zixu Zhu, Yanpeng Wang, Peng Qin, Chengzhi Liang, Daowen Wang, Jin-Long Qiu, Feng Zhang, Caixia Gao |
英文第一作者: |
Shuai Jin, Yuan Zong, Qiang Gao, Zixu Zhu, Yanpeng Wang, Peng Qin, Chengzhi Liang, Daowen Wang, Jin-Long Qiu, Feng Zhang, Caixia Gao |
联系作者: |
|
英文联系作者: |
|
外单位作者单位: |
|
英文外单位作者单位: |
|
发表年度: |
2019-03-01 |
卷: |
|
期: |
|
页码: |
|
摘要: |
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 (WGS) analysis of rice plants treated with 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. |
英文摘要: |
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 (WGS) analysis of rice plants treated with 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. |
刊物名称: |
Science |
英文刊物名称: |
Science |
论文全文: |
|
英文论文全文: |
|
全文链接: |
|
其它备注: |
Shuai Jin, Yuan Zong, Qiang Gao, Zixu Zhu, Yanpeng Wang, Peng Qin, Chengzhi Liang, Daowen Wang, Jin-Long Qiu, Feng Zhang, Caixia Gao. Cytosine, But not Adenine, Base Editors Induce Genome-wide Off-target Mutations in Rice. Science. DOI:10.1126/science.aaw7166 |
英文其它备注: |
|
学科: |
|
英文学科: |
|
影响因子: |
|
第一作者所在部门: |
|
英文第一作者所在部门: |
|
论文出处: |
|
英文论文出处: |
|
论文类别: |
|
英文论文类别: |
|
参与作者: |
|
英文参与作者: |
|
|