Off-target challenge for base editor-mediated genome editing
Off-target challenge for base editor-mediated genome editing
复制标题
碱基编辑器介导的基因组编辑的脱靶挑战
DOI：
10.1007/s10565-019-09474-8
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发表时间：
2019-04
影响因子：
6.1
通讯作者：
Huang Junjiu
中科院分区：
文献类型：
--
作者：
Liang Puping;Huang Junjiu
Genome editing is a revolutionary technology that holds immense promise for creating livestock or crops with improved traits and curing incurable inherited diseases by correcting genomic DNA mutation. The past decade has witnessed rapid developments of genome editing tools, such as zinc finger nuclease (ZFN), TALEN nuclease, and CRISPR/Cas nuclease. These programmable nucleases have been utilized to edit the genome by inducing DNA double-strand break (DSB), which will be then repaired by either non-homologous end joining (NHEJ) or homology directed repair (HDR). However, the efficiency of HDR is still low, and DSB poses a significant threat to genome stability, whose dysregulation might result in a serious disease like cancer. To tackle these issues, new genome editing tools, named base editors, which could catalyze highly efficient base deamination-induced base transition without inducing DSB were developed (Gaudelli et al. 2017; Nishida et al. 2016; Komor et al. 2016). There are two types of base editors, cytidine base editor (CBE, C-to-T transition) and adenine base editor (ABE, A-to-G transition). CBE, composed of rAPOBEC1: nCas9: UGI effector and gRNA, harnesses rAPOBEC1 to deaminate cytidine (C) on the non-target strand and nCas9 (nickase Cas9) to cleave the target strand. ABE, composed of TADA: TADA*: nCas9 effector and gRNA, utilizes TADA to deaminate adenine (A) on the non-target strand and nCas9 to cleave the target strand. Without inducing DSB, such programmed Bchemical surgery^ on DNA was supposed to be more precise and efficient. Recently, both our group and Kim et al. developed in vitro assays (EndoV-seq and Digenome-seq) to investigate the genome-wide specificity of CBE and ABE, which could detect the gRNA-dependent off-target of base editors. We found that CBE and ABE were much more specific than Cas9 nuclease (Kim et al. 2017a, 2019; Liang et al. 2019). However, both EndoV-seq and Digenome-seq might underestimate the off-target effects of base editors, because they could not detect offtarget deamination independent of gRNA recognition and nCas9 cleavage that might occur in vitro and in vivo (Kim et al. 2017a, 2019; Liang et al. 2019). Recently, Zuo et al. and Jin et al. independently devised experiments to profile the genome-wide specificity of CBE, ABE, and Cas9 nuclease in mouse embryo or rice (Zuo et al. 2019; Jin et al. 2019). Previous attempts to detect genome-wide off-target effects of genome editing tools, especially for the single-nucleotide variations (SNVs), were hampered by genetic heterogeneity of individual organism, spontaneous mutation rate, the coverage of whole genome amplification, whole genome
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影响因子：
46.9
作者：
Kim YB;Komor AC;Levy JM;Packer MS;Zhao KT;Liu DR
通讯作者：
Liu DR
影响因子：
16.6
作者：
Rees HA;Komor AC;Yeh WH;Caetano-Lopes J;Warman M;Edge ASB;Liu DR
通讯作者：
Liu DR
影响因子：
64.8
作者：
Komor AC;Kim YB;Packer MS;Zuris JA;Liu DR
通讯作者：
Liu DR
影响因子：
46.9
作者：
Kim, Daesik;Lim, Kayeong;Kim, Jin-Soo
通讯作者：
Kim, Jin-Soo
影响因子：
16.6
作者：
Yang, Luhan;Grishin, Dennis;Wang, Gang;Aach, John;Zhang, Cheng-Zhong;Chari, Raj;Homsy, Jason;Cai, Xuyu;Zhao, Yue;Fan, Jian-Bing;Seidman, Christine;Seidman, Jonathan;Pu, William;Church, George
通讯作者：
Church, George