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![]() |
刊名 | CELL REPORTS
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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 |
DOI | 10.1016/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
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