CA2757178C - Mutants of activation-induced cytidine deaminase (aid) and methods of use - Google Patents
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- C07K—PEPTIDES
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- C12Y—ENZYMES
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- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
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Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007067032A1 (en) | 2005-12-09 | 2007-06-14 | Academisch Medisch Cemtrum Bij De Universiteit Van Amsterdam | Means and methods for influencing the stability of cells |
| CA3015416C (en) | 2005-12-09 | 2022-10-11 | Academisch Medisch Centrum Bij De Universiteit Van Amsterdam | Means and methods for influencing the stability of antibody producing cells |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| DK2792236T4 (da) | 2009-07-08 | 2023-05-15 | Kymab Ltd | Dyremodeller og terapeutiske molekyler |
| ES2666584T3 (es) * | 2009-07-15 | 2018-05-07 | Aimm Therapeutics B.V. | Medios y métodos para producir anticuerpos de alta afinidad |
| EP2638155A1 (en) | 2010-11-08 | 2013-09-18 | Kymab Limited | Cells & vertebrates for enhanced somatic hypermutation and class switch recombination |
| RU2585153C2 (ru) | 2010-12-02 | 2016-05-27 | Аимм Терапьютикс Б.В. | Средства и способы получения высокоаффинных антител |
| EP2670848B1 (en) | 2011-02-06 | 2016-02-03 | Yeda Research and Development Co. Ltd | Affinity maturated t cell receptors and use thereof |
| BR112014006394A2 (pt) | 2011-09-19 | 2017-03-28 | Kymab Ltd | manipulação de diversidade genética de imunoglobulina e terapêuticos multi-anticorpos |
| WO2013045916A1 (en) | 2011-09-26 | 2013-04-04 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
| GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| CN103031295B (zh) * | 2012-12-10 | 2015-01-28 | 浙江工业大学 | 冬虫夏草胞苷脱氨酶、编码基因及其应用 |
| PL225333B1 (pl) * | 2013-01-14 | 2017-03-31 | Inst Chemii Bioorganicznej Polskiej Akademii Nauk | Preparat wykazujący aktywność ludzkiej deaminazy cytydyny indukowanej aktywacją limfocytów B (AID) oraz sposób otrzymywania tego preparatu w systemie bakteryjnym |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| US9783618B2 (en) | 2013-05-01 | 2017-10-10 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| CA2925723A1 (en) | 2013-10-01 | 2015-04-09 | Kymab Limited | Animal models and therapeutic molecules |
| DK3099709T3 (da) | 2014-01-31 | 2020-02-03 | Aimm Therapeutics Bv | Midler og fremgangsmåder til fremstilling af stabile antistoffer |
| CN104263755B (zh) * | 2014-07-03 | 2017-02-15 | 成都中联生科基因科技有限公司 | 一种利用dna损伤修复机制使单克隆抗体细胞株进行体内快速进化的新方法 |
| US10968444B2 (en) * | 2017-05-22 | 2021-04-06 | Abzyme Therapeutics Llc | Methods for generating bispecific functional agents |
| US10704040B2 (en) * | 2017-05-22 | 2020-07-07 | Abzyme Therapeutics Llc | Triple-mode system for antibody maturation, surface display and secretion |
| CN107177625B (zh) * | 2017-05-26 | 2021-05-25 | 中国农业科学院植物保护研究所 | 一种定点突变的人工载体系统及定点突变方法 |
| US10961525B2 (en) * | 2017-07-05 | 2021-03-30 | The Trustees Of The University Of Pennsylvania | Hyperactive AID/APOBEC and hmC dominant TET enzymes |
| CN109402096B (zh) * | 2018-11-20 | 2021-01-01 | 中国科学院生物物理研究所 | 一种aid酶突变体及其应用 |
| WO2020148206A1 (en) * | 2019-01-14 | 2020-07-23 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and kits for generating and selecting a variant of a binding protein with increased binding affinity and/or specificity |
| WO2020206325A2 (en) * | 2019-04-05 | 2020-10-08 | The Broad Institute, Inc. | A pseudo-random dna editor for efficient and continuous nucleotide diversification in human cells |
| CN110734900B (zh) * | 2019-11-06 | 2022-09-30 | 上海科技大学 | 一种胞嘧啶碱基编辑工具及其用途 |
| CN111518794B (zh) * | 2020-04-13 | 2023-05-16 | 中山大学 | 基于激活诱导性胞苷脱氨酶的诱导突变蛋白的制备和用途 |
| IL276599A (en) | 2020-08-09 | 2022-03-01 | Yeda Res & Dev | T cell receptor unique to mage-a1 and its uses |
| CN112708650A (zh) * | 2020-12-31 | 2021-04-27 | 河南巨龙生物工程股份有限公司 | 一种缩短胞苷发酵迟滞期的方法 |
| CN113073094B (zh) * | 2021-03-29 | 2023-03-28 | 中山大学 | 基于胞苷脱氨酶LjCDA1L1_4a及其突变体的单碱基突变系统 |
| CN115094127A (zh) * | 2022-02-22 | 2022-09-23 | 中国科学院深圳先进技术研究院 | 一种原位检测蛋白质与脱氧核糖核苷酸结合位置的方法 |
| EP4491723A1 (en) * | 2022-03-08 | 2025-01-15 | Institute Of Genetics And Developmental Biology, Chinese Academy Of Sciences | Cytosine deaminase and use thereof in base editing |
| WO2025119295A1 (zh) * | 2023-12-05 | 2025-06-12 | 广州瑞风生物科技有限公司 | 脱氨酶、融合蛋白、核酸、药物组合物及其应用 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4737462A (en) | 1982-10-19 | 1988-04-12 | Cetus Corporation | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of interferon-β |
| US4518584A (en) | 1983-04-15 | 1985-05-21 | Cetus Corporation | Human recombinant interleukin-2 muteins |
| JPS61135597A (ja) * | 1984-12-06 | 1986-06-23 | Takeda Chem Ind Ltd | シチジンおよびデオキシシチジンの製造法 |
| CA1293460C (en) | 1985-10-07 | 1991-12-24 | Brian Lee Sauer | Site-specific recombination of dna in yeast |
| US5583024A (en) | 1985-12-02 | 1996-12-10 | The Regents Of The University Of California | Recombinant expression of Coleoptera luciferase |
| GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
| US5221623A (en) | 1986-07-22 | 1993-06-22 | Boyce Thompson Institute For Plant Research, Inc. | Use of bacterial luciferase structural genes for cloning and monitoring gene expression in microorganisms and for tagging and identification of genetically engineered organisms |
| US4937190A (en) | 1987-10-15 | 1990-06-26 | Wisconsin Alumni Research Foundation | Translation enhancer |
| US5070012A (en) | 1988-03-30 | 1991-12-03 | The Board Of Trustees Of The Leland Stanford Junior University | Monitoring of cells and trans-activating transcription elements |
| US5683888A (en) | 1989-07-22 | 1997-11-04 | University Of Wales College Of Medicine | Modified bioluminescent proteins and their use |
| US5283179A (en) | 1990-09-10 | 1994-02-01 | Promega Corporation | Luciferase assay method |
| CA2096222C (en) | 1990-11-13 | 1998-12-29 | Stephen D. Lupton | Bifunctional selectable fusion genes |
| WO1992015694A1 (en) | 1991-03-08 | 1992-09-17 | The Salk Institute For Biological Studies | Flp-mediated gene modification in mammalian cells, and compositions and cells useful therefor |
| GB9116601D0 (en) * | 1991-08-01 | 1991-09-18 | Iaf Biochem Int | 1,3-oxathiolane nucleoside analogues |
| US5770428A (en) | 1993-02-17 | 1998-06-23 | Wisconsin Alumni Research Foundation | Chimeric retrovial expression vectors and particles containing a simple retroviral long terminal repeat, BLV or HIV coding regions and cis-acting regulatory sequences, and an RNA translational enhancer with internal ribsome entry site |
| AU6953394A (en) | 1993-05-21 | 1994-12-20 | Targeted Genetics Corporation | Bifunctional selectable fusion genes based on the cytosine deaminase (cd) gene |
| US5464758A (en) | 1993-06-14 | 1995-11-07 | Gossen; Manfred | Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters |
| US5814618A (en) | 1993-06-14 | 1998-09-29 | Basf Aktiengesellschaft | Methods for regulating gene expression |
| JP3466765B2 (ja) | 1994-07-27 | 2003-11-17 | キッコーマン株式会社 | ビオチン化ホタルルシフェラーゼ、ビオチン化ホタルルシフェラーゼ遺伝子、新規な組み換え体ｄｎａ、ビオチン化ホタルルシフェラーゼの製造法及び生物発光分析法 |
| US5741657A (en) | 1995-03-20 | 1998-04-21 | The Regents Of The University Of California | Fluorogenic substrates for β-lactamase and methods of use |
| US5885827A (en) | 1996-01-23 | 1999-03-23 | The Regents Of The Universtiy Of California | Eukaryotic high rate mutagenesis system |
| US5955604A (en) | 1996-10-15 | 1999-09-21 | The Regents Of The University Of California | Substrates for β-lactamase and uses thereof |
| CA2365601A1 (en) * | 1999-03-29 | 2000-10-05 | Kansai Technology Licensing Organization Co., Ltd. | Novel cytidine deaminase |
| FR2814642B1 (fr) | 2000-10-03 | 2005-07-01 | Ass Pour Le Dev De La Rech En | Souris transgenique pour la recombinaison ciblee mediee par la cre-er modifiee |
| US20040142325A1 (en) * | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
| EP1506288B1 (en) * | 2002-05-10 | 2013-04-17 | Medical Research Council | Activation induced deaminase (aid) |
| US20050287648A1 (en) * | 2002-08-05 | 2005-12-29 | University Of Rochester | Protein Transducing Domain/Deaminase Chimeric Proteins, Related Compounds, and Uses Thereof |
| US7393923B2 (en) | 2004-11-08 | 2008-07-01 | The Regents Of The University Of California | Red-shifted fluorescent proteins mPlum and mRaspberry and polynucleotides encoding the same |
| JP4482693B2 (ja) * | 2005-08-29 | 2010-06-16 | 国立大学法人 岡山大学 | 抗体産生細胞の特異的選択方法 |
| GB0607063D0 (en) * | 2006-04-07 | 2006-05-17 | Cellcentric Ltd | Compositions and methods for epigenetic modification of nucleic acid sequences in vivo |
| US20090075378A1 (en) * | 2007-02-20 | 2009-03-19 | Anaptysbio, Inc. | Somatic hypermutation systems |
| US7803582B2 (en) * | 2007-03-17 | 2010-09-28 | Hongzhan Xu | Recombinant vector and use in gene therapy |
| US8095350B2 (en) * | 2007-12-21 | 2012-01-10 | Xiaojiang Chen | Three-dimensional structure of the APOBEC 2 structure, uses thereof, and methods for treating chronic and infectious diseases |
| US7981655B2 (en) * | 2008-02-07 | 2011-07-19 | Regents Of The University Of Minnesota | Modified cytosine deaminases |
| EP2098536A1 (en) * | 2008-03-05 | 2009-09-09 | 4-Antibody AG | Isolation and identification of antigen- or ligand-specific binding proteins |
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| AU2010230985B2 (en) | 2015-09-24 |
| JP5683566B2 (ja) | 2015-03-11 |
| CN102482639B (zh) | 2016-01-06 |
| US20120151613A1 (en) | 2012-06-14 |
| CA2757178A1 (en) | 2010-10-07 |
| EP2414507A1 (en) | 2012-02-08 |
| US9683226B2 (en) | 2017-06-20 |
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