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Literature DB >> 32424272

A rationally engineered cytosine base editor retains high on-target activity while reducing both DNA and RNA off-target effects.

Erwei Zuo^1,2, Yidi Sun^3,4, Tanglong Yuan⁵, Bingbing He⁶, Changyang Zhou⁶, Wenqin Ying⁶, Jing Liu⁵, Wu Wei^4,7, Rong Zeng^3,8, Yixue Li^9,10,11,12, Hui Yang^13,14.

Abstract

Cytosine base editors (CBEs) offer a powerful tool for correcting point mutations, yet their DNA and RNA off-target activities have caused concerns in biomedical applications. We describe screens of 23 rationally engineered CBE variants, which reveal mutation residues in the predicted DNA-binding site can dramatically decrease the Cas9-independent off-target effects. Furthermore, we obtained a CBE variant-YE1-BE3-FNLS-that retains high on-target editing efficiency while causing extremely low off-target edits and bystander edits.

Entities: Chemical

Mesh：

Substances：

Year: 2020 PMID： 32424272 DOI： 10.1038/s41592-020-0832-x

Source DB: PubMed Journal: Nat Methods ISSN： 1548-7091 Impact factor: 28.547

1 in total

1. Mutational analysis of apolipoprotein B mRNA editing enzyme (APOBEC1). structure-function relationships of RNA editing and dimerization.

Authors: B B Teng; S Ochsner; Q Zhang; K V Soman; P P Lau; L Chan
Journal: J Lipid Res Date: 1999-04 Impact factor: 5.922

1 in total

26 in total

1. Sequence-specific prediction of the efficiencies of adenine and cytosine base editors.

Authors: Myungjae Song; Hui Kwon Kim; Sungtae Lee; Younggwang Kim; Sang-Yeon Seo; Jinman Park; Jae Woo Choi; Hyewon Jang; Jeong Hong Shin; Seonwoo Min; Zhejiu Quan; Ji Hun Kim; Hoon Chul Kang; Sungroh Yoon; Hyongbum Henry Kim
Journal: Nat Biotechnol Date: 2020-07-06 Impact factor: 54.908

2. Programmable C-to-U RNA editing using the human APOBEC3A deaminase.

Authors: Xinxin Huang; Junjun Lv; Yongqin Li; Shaoshuai Mao; Zhifang Li; Zhengyu Jing; Yidi Sun; Xiaoming Zhang; Shengxi Shen; Xinxin Wang; Minghui Di; Jianyang Ge; Xingxu Huang; Erwei Zuo; Tian Chi
Journal: EMBO J Date: 2020-10-15 Impact factor: 11.598

Review 3. Improvement of base editors and prime editors advances precision genome engineering in plants.

Authors: Kai Hua; Peijin Han; Jian-Kang Zhu
Journal: Plant Physiol Date: 2022-03-28 Impact factor: 8.340

Review 4. CRISPR-derived genome editing therapies: Progress from bench to bedside.

Authors: Holly A Rees; Alex C Minella; Cameron A Burnett; Alexis C Komor; Nicole M Gaudelli
Journal: Mol Ther Date: 2021-10-05 Impact factor: 11.454

5. Detect-seq reveals out-of-protospacer editing and target-strand editing by cytosine base editors.

Authors: Zhixin Lei; Haowei Meng; Zhicong Lv; Menghao Liu; Huanan Zhao; Hao Wu; Xiaoxue Zhang; Lulu Liu; Yuan Zhuang; Kailin Yin; Yongchang Yan; Chengqi Yi
Journal: Nat Methods Date: 2021-06-07 Impact factor: 28.547

Review 6. Genetic therapies for the first molecular disease.

Authors: Phillip A Doerfler; Akshay Sharma; Jerlym S Porter; Yan Zheng; John F Tisdale; Mitchell J Weiss
Journal: J Clin Invest Date: 2021-04-15 Impact factor: 14.808

7. Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations.

Authors: Lijie Wang; Wei Xue; Hongxia Zhang; Runze Gao; Houyuan Qiu; Jia Wei; Lina Zhou; Yun-Ni Lei; Xiaocheng Wu; Xiao Li; Chengfang Liu; Jing Wu; Qiubing Chen; Hanhui Ma; Xingxu Huang; Cheguo Cai; Ying Zhang; Bei Yang; Hao Yin; Li Yang; Jia Chen
Journal: Nat Cell Biol Date: 2021-05-10 Impact factor: 28.824