中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Intrinsic Nucleotide Preference of Diversifying Base Editors Guides Antibody Ex Vivo Affinity Maturation

文献类型:期刊论文

作者Liu, Liu Daisy1; Huang, Min1; Dai, Pengfei1; Liu, Tingting1; Fan, Shuangshuang1; Meng, Fei-Long1; Cheng, Xueqian2; Zhao, Yaofeng2; Yeap, Leng-Siew3
刊名CELL REPORTS
出版日期2018
卷号25期号:4页码:884-+
关键词Induced Cytidine Deaminase Class Switch Recombination Somatic Hypermutation Neutralizing Antibodies Genomic Instability Eukaryotic Genomes Structural Basis Mammalian-cells Super-enhancers Dna Cleavage
ISSN号2211-1247
DOI10.1016/j.celrep.2018.09.090
文献子类Article
英文摘要

Base editors (BEs) are emerging tools used for precision correction or diversifying mutation. It provides a potential way to recreate somatic hypermutations (SHM) for generating high-affinity antibody, which is usually screened from antigen-challenged animal models or synthetic combinatorial libraries. By comparing somatic mutations in the same genomic context, we screened engineered deaminases and CRISPR-deaminase coupling approaches and updated diversifying base editors (DBEs) to generate SHM. The deaminase used in DBEs retains its intrinsic nucleotide preference and mutates cytidines at its preferred motifs. DBE with AID targets the same hotspots as physiological AID does in vivo, while DBE with other deaminases generates distinct mutation profiles from the same DNA substrate. Down-stream DNA repair pathways further diversified the sequence, while Cas9-nickase restricted mutation spreading. Finally, application of DBE in an antibody display system achieved antibody affinity maturation ex vivo. Our findings provide insight of DBE working mechanism and an alternative antibody engineering approach.

WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000448219500008
版本出版稿
源URL[http://202.127.25.143/handle/331003/3430]  
专题生化所2018年发文
通讯作者Meng, Fei-Long
作者单位1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,Ctr Excellence Mol Cell Sc, 320 Yueyang Rd, Shanghai 200031, Peoples R China;
2.China Agr Univ, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China;
3.Shanghai Jiao Tong Univ, Sch Med, Dept Immunol & Microbiol, Shanghai Inst Immunol, Shanghai 200025, Peoples R China
推荐引用方式
GB/T 7714
Liu, Liu Daisy,Huang, Min,Dai, Pengfei,et al. Intrinsic Nucleotide Preference of Diversifying Base Editors Guides Antibody Ex Vivo Affinity Maturation[J]. CELL REPORTS,2018,25(4):884-+.
APA Liu, Liu Daisy.,Huang, Min.,Dai, Pengfei.,Liu, Tingting.,Fan, Shuangshuang.,...&Yeap, Leng-Siew.(2018).Intrinsic Nucleotide Preference of Diversifying Base Editors Guides Antibody Ex Vivo Affinity Maturation.CELL REPORTS,25(4),884-+.
MLA Liu, Liu Daisy,et al."Intrinsic Nucleotide Preference of Diversifying Base Editors Guides Antibody Ex Vivo Affinity Maturation".CELL REPORTS 25.4(2018):884-+.

入库方式: OAI收割

来源:上海生物化学与细胞生物学研究所

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