IL266681B2 - Polynucleotide libraries with controlled stoichiometry and their synthesis - Google Patents
Polynucleotide libraries with controlled stoichiometry and their synthesisInfo
- Publication number
- IL266681B2 IL266681B2 IL266681A IL26668119A IL266681B2 IL 266681 B2 IL266681 B2 IL 266681B2 IL 266681 A IL266681 A IL 266681A IL 26668119 A IL26668119 A IL 26668119A IL 266681 B2 IL266681 B2 IL 266681B2
- Authority
- IL
- Israel
- Prior art keywords
- polynucleotides
- polynucleotide
- library
- percent
- instances
- Prior art date
Links
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Classifications
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1093—General methods of preparing gene libraries, not provided for in other subgroups
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
- C12Q1/6837—Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
- C12Q1/6874—Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Molecular Biology (AREA)
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- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Computational Biology (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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| US201762558666P | 2017-09-14 | 2017-09-14 | |
| PCT/US2017/062391 WO2018094263A1 (en) | 2016-11-18 | 2017-11-17 | Polynucleotide libraries having controlled stoichiometry and synthesis thereof |
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| IL266681A IL266681A (en) | 2019-07-31 |
| IL266681B1 IL266681B1 (en) | 2024-09-01 |
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| IL266681A IL266681B2 (en) | 2016-11-18 | 2017-11-17 | Polynucleotide libraries with controlled stoichiometry and their synthesis |
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| IL314890A IL314890A (en) | 2016-11-18 | 2017-11-17 | Polynucleotide libraries having controlled stoichiometry and synthesis thereof |
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| US (2) | US20180142289A1 (OSRAM) |
| EP (1) | EP3541973B1 (OSRAM) |
| JP (3) | JP2020504709A (OSRAM) |
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| CN (1) | CN110382752A (OSRAM) |
| AU (2) | AU2017363204B2 (OSRAM) |
| CA (1) | CA3044057A1 (OSRAM) |
| GB (1) | GB2572877A (OSRAM) |
| IL (2) | IL314890A (OSRAM) |
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| WO2016126882A1 (en) | 2015-02-04 | 2016-08-11 | Twist Bioscience Corporation | Methods and devices for de novo oligonucleic acid assembly |
| WO2016172377A1 (en) | 2015-04-21 | 2016-10-27 | Twist Bioscience Corporation | Devices and methods for oligonucleic acid library synthesis |
| EP3350314A4 (en) | 2015-09-18 | 2019-02-06 | Twist Bioscience Corporation | OLIGONUCLEIC ACID VARIANT LIBRARIES VARIANT AND SYNTHESIS THEREOF |
| CN108698012A (zh) | 2015-09-22 | 2018-10-23 | 特韦斯特生物科学公司 | 用于核酸合成的柔性基底 |
| CN108603307A (zh) | 2015-12-01 | 2018-09-28 | 特韦斯特生物科学公司 | 功能化表面及其制备 |
| AU2017261189B2 (en) * | 2016-05-02 | 2023-02-09 | Becton, Dickinson And Company | Accurate molecular barcoding |
| GB2568444A (en) | 2016-08-22 | 2019-05-15 | Twist Bioscience Corp | De novo synthesized nucleic acid libraries |
| US10417457B2 (en) | 2016-09-21 | 2019-09-17 | Twist Bioscience Corporation | Nucleic acid based data storage |
| JP2020504709A (ja) * | 2016-11-18 | 2020-02-13 | ツイスト バイオサイエンス コーポレーション | 制御された化学量論を有するポリヌクレオチドライブラリおよびその合成 |
| CN110366613A (zh) | 2016-12-16 | 2019-10-22 | 特韦斯特生物科学公司 | 免疫突触的变体文库及其合成 |
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| CN110913865A (zh) | 2017-03-15 | 2020-03-24 | 特韦斯特生物科学公司 | 免疫突触的变体文库及其合成 |
| WO2018231864A1 (en) | 2017-06-12 | 2018-12-20 | Twist Bioscience Corporation | Methods for seamless nucleic acid assembly |
| KR102784398B1 (ko) | 2017-06-12 | 2025-03-19 | 트위스트 바이오사이언스 코포레이션 | 심리스 핵산 어셈블리를 위한 방법 |
| JP2020536504A (ja) | 2017-09-11 | 2020-12-17 | ツイスト バイオサイエンス コーポレーション | Gpcr結合タンパク質およびその合成 |
| KR102889470B1 (ko) | 2017-10-20 | 2025-11-21 | 트위스트 바이오사이언스 코포레이션 | 폴리뉴클레오타이드 합성을 위한 가열된 나노웰 |
| WO2019136175A1 (en) | 2018-01-04 | 2019-07-11 | Twist Bioscience Corporation | Dna-based digital information storage |
| CA3100739A1 (en) | 2018-05-18 | 2019-11-21 | Twist Bioscience Corporation | Polynucleotides, reagents, and methods for nucleic acid hybridization |
| CN119708086A (zh) | 2018-12-26 | 2025-03-28 | 特韦斯特生物科学公司 | 高度准确的从头多核苷酸合成 |
| AU2020227802A1 (en) | 2019-02-26 | 2021-10-14 | Twist Bioscience Corporation | Variant nucleic acid libraries for antibody optimization |
| EP3930753A4 (en) | 2019-02-26 | 2023-03-29 | Twist Bioscience Corporation | VARIANT NUCLEIC ACID LIBRARIES FOR GLP1 RECEPTOR |
| CN114729342A (zh) | 2019-06-21 | 2022-07-08 | 特韦斯特生物科学公司 | 基于条形码的核酸序列装配 |
| WO2021061829A1 (en) | 2019-09-23 | 2021-04-01 | Twist Bioscience Corporation | Variant nucleic acid libraries for crth2 |
| AU2020355027A1 (en) | 2019-09-23 | 2022-04-21 | Twist Bioscience Corporation | Antibodies that bind CD3 Epsilon |
| WO2021092244A1 (en) * | 2019-11-06 | 2021-05-14 | Adaptive Biotechnologies Corporation | Synthetic strands for nucleic acid sequencing and related methods and systems |
| CN110853708B (zh) * | 2019-11-13 | 2022-03-08 | 上海仁东医学检验所有限公司 | 用于hla分型的核酸捕获探针的设计方法 |
| BR112022021789A2 (pt) | 2020-04-27 | 2023-03-07 | Twist Bioscience Corp | Bibliotecas de ácido nucléico variantes para coronavírus |
| EP4150110A4 (en) * | 2020-05-11 | 2024-06-26 | Personal Genome Diagnostics Inc. | SELECTIVE CAPTURE OF TARGET DNA SEQUENCES |
| CN115867672A (zh) * | 2020-05-28 | 2023-03-28 | 伊鲁米纳公司 | 比较具有不同特征的多核苷酸拷贝 |
| KR20230074151A (ko) | 2020-08-26 | 2023-05-26 | 트위스트 바이오사이언스 코포레이션 | Glp1r 변이체에 관한 방법 및 조성물 |
| WO2022086866A1 (en) | 2020-10-19 | 2022-04-28 | Twist Bioscience Corporation | Methods of synthesizing oligonucleotides using tethered nucleotides |
| CA3206018A1 (en) | 2021-01-21 | 2022-07-28 | Twist Bioscience Corporation | Methods and compositions relating to adenosine receptors |
| BE1029144B1 (fr) * | 2021-02-25 | 2022-09-20 | Oncodna | Méthode de caracterisation d'une tumeur à l'aide d'un séquençage ciblé |
| US12258406B2 (en) | 2021-03-24 | 2025-03-25 | Twist Bioscience Corporation | Antibodies that bind CD3 Epsilon |
| US12201857B2 (en) | 2021-06-22 | 2025-01-21 | Twist Bioscience Corporation | Methods and compositions relating to covid antibody epitopes |
| KR20240101677A (ko) | 2021-11-18 | 2024-07-02 | 트위스트 바이오사이언스 코포레이션 | Dickkopf-1 변이체 항체 및 사용 방법 |
| US12325739B2 (en) | 2022-01-03 | 2025-06-10 | Twist Bioscience Corporation | Bispecific SARS-CoV-2 antibodies and methods of use |
| CN116417071A (zh) * | 2023-04-07 | 2023-07-11 | 祥符实验室 | 一种dna数据存储的选择性访问方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5474796A (en) | 1991-09-04 | 1995-12-12 | Protogene Laboratories, Inc. | Method and apparatus for conducting an array of chemical reactions on a support surface |
| JP2005535283A (ja) * | 2001-11-13 | 2005-11-24 | ルビコン ゲノミクス インコーポレイテッド | ランダムフラグメント化により生成されたdna分子を用いたdna増幅および配列決定 |
| US9598737B2 (en) * | 2012-05-09 | 2017-03-21 | Longhorn Vaccines And Diagnostics, Llc | Next generation genomic sequencing methods |
| WO2010030683A1 (en) * | 2008-09-09 | 2010-03-18 | Rosetta Inpharmatics Llc | Methods of generating gene specific libraries |
| US8828688B2 (en) * | 2010-05-27 | 2014-09-09 | Affymetrix, Inc. | Multiplex amplification methods |
| EP2670894B1 (en) * | 2011-02-02 | 2017-11-29 | University Of Washington Through Its Center For Commercialization | Massively parallel continguity mapping |
| AU2013251701A1 (en) * | 2012-04-24 | 2014-10-30 | Gen9, Inc. | Methods for sorting nucleic acids and multiplexed preparative in vitro cloning |
| US20150197787A1 (en) * | 2012-08-02 | 2015-07-16 | Qiagen Gmbh | Recombinase mediated targeted dna enrichment for next generation sequencing |
| CN105518151B (zh) * | 2013-03-15 | 2021-05-25 | 莱兰斯坦福初级大学评议会 | 循环核酸肿瘤标志物的鉴别和用途 |
| KR102122632B1 (ko) | 2013-08-05 | 2020-06-16 | 트위스트 바이오사이언스 코포레이션 | 드 노보 합성된 유전자 라이브러리 |
| EP3039161B1 (en) * | 2013-08-30 | 2021-10-06 | Personalis, Inc. | Methods and systems for genomic analysis |
| EP3063301A4 (en) * | 2013-10-29 | 2017-07-19 | Longhorn Vaccines and Diagnostics, LLC | Next generation genomic sequencing methods |
| JP2020504709A (ja) * | 2016-11-18 | 2020-02-13 | ツイスト バイオサイエンス コーポレーション | 制御された化学量論を有するポリヌクレオチドライブラリおよびその合成 |
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