TY - JOUR
T1 - Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice
AU - Jin, Shuai
AU - Zong, Yuan
AU - Gao, Qiang
AU - Zhu, Zixu
AU - Wang, Yanpeng
AU - Qin, Peng
AU - Liang, Chengzhi
AU - Wang, Daowen
AU - Qiu, Jin Long
AU - Zhang, Feng
AU - Gao, Caixia
N1 - Publisher Copyright:
© 2019 American Association for the Advancement of Science. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1126/science.aaw7166
DO - 10.1126/science.aaw7166
M3 - Article
C2 - 30819931
AN - SCOPUS:85063014306
SN - 0036-8075
VL - 364
SP - 292
EP - 295
JO - Science
JF - Science
IS - 6437
ER -