ES2634428T3 - Amplificación de ácido nucleico con supresión específica de alelo de variantes de secuencia - Google Patents
Amplificación de ácido nucleico con supresión específica de alelo de variantes de secuencia Download PDFInfo
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- ES2634428T3 ES2634428T3 ES10700205.7T ES10700205T ES2634428T3 ES 2634428 T3 ES2634428 T3 ES 2634428T3 ES 10700205 T ES10700205 T ES 10700205T ES 2634428 T3 ES2634428 T3 ES 2634428T3
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- oligonucleotide
- target sequence
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- nucleic acid
- amplification
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- 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
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6858—Allele-specific amplification
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| ES2662825T3 (es) | 2013-02-25 | 2018-04-09 | Seegene, Inc. | Detección de variación de nucleótido en una secuencia de ácidos nucleicos diana |
| US20160244816A1 (en) | 2013-07-15 | 2016-08-25 | Seegene, Inc. | Detection of target nucleic acid sequence by pto cleavage and extension-dependent immobilized oligonucleotide hybridization |
| US10913977B2 (en) | 2013-07-24 | 2021-02-09 | Dana-Farber Cancer Institute, Inc. | Methods and compositions to enable enrichment of minor DNA alleles by limiting denaturation time in PCR or simply enable enrichment of minor DNA alleles by limiting the denaturation time in PCR |
| WO2015057008A2 (en) | 2013-10-18 | 2015-04-23 | Seegene, Inc. | Detection of target nucleic acid sequence on solid phase by pto cleavage and extension using hcto assay |
| CN105283555A (zh) | 2013-10-20 | 2016-01-27 | 特罗瓦基因公司 | 核酸序列的合成和富集 |
| EP4512908A3 (en) * | 2014-05-19 | 2025-03-26 | William Marsh Rice University | Allele-specific amplification using a composition of overlapping non-allele-specific primer and allele-specific blocker oligonucleotides |
| JP5813263B1 (ja) * | 2015-03-31 | 2015-11-17 | 日鉄住金環境株式会社 | 遺伝子変異の検出方法及びそれに用いる蛍光標識オリゴヌクレオチド |
| US11371090B2 (en) | 2016-12-12 | 2022-06-28 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for molecular barcoding of DNA molecules prior to mutation enrichment and/or mutation detection |
| US11174511B2 (en) | 2017-07-24 | 2021-11-16 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for selecting and amplifying DNA targets in a single reaction mixture |
| CN117858956A (zh) * | 2021-08-25 | 2024-04-09 | 南京金斯瑞生物科技有限公司 | 一种用于检测单碱基突变的引物组和基因芯片方法 |
| US20240401122A1 (en) * | 2021-09-13 | 2024-12-05 | Nexgen Cancer Detection Llc | Methods for detecting a target polynucleotide in a sample |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
| US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| DE3529478A1 (de) | 1985-08-16 | 1987-02-19 | Boehringer Mannheim Gmbh | 7-desaza-2'desoxyguanosin-nukleotide, verfahren zu deren herstellung und deren verwendung zur nukleinsaeure-sequenzierung |
| US5405774A (en) | 1986-08-22 | 1995-04-11 | Hoffmann-La Roche Inc. | DNA encoding a mutated thermostable nucleic acid polymerase enzyme from thermus species sps17 |
| US5466591A (en) | 1986-08-22 | 1995-11-14 | Hoffmann-La Roche Inc. | 5' to 3' exonuclease mutations of thermostable DNA polymerases |
| US5455170A (en) | 1986-08-22 | 1995-10-03 | Hoffmann-La Roche Inc. | Mutated thermostable nucleic acid polymerase enzyme from Thermus species Z05 |
| US5795762A (en) | 1986-08-22 | 1998-08-18 | Roche Molecular Systems, Inc. | 5' to 3' exonuclease mutations of thermostable DNA polymerases |
| US5374553A (en) | 1986-08-22 | 1994-12-20 | Hoffmann-La Roche Inc. | DNA encoding a thermostable nucleic acid polymerase enzyme from thermotoga maritima |
| US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| US5386023A (en) | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
| ATE197718T1 (de) | 1990-09-28 | 2000-12-15 | Hoffmann La Roche | Gereinigte thermostabile nukleinsäurepolymerase aus thermosipho africanus |
| JPH04234422A (ja) | 1990-10-31 | 1992-08-24 | Internatl Business Mach Corp <Ibm> | 二重硬化エポキシバックシール処方物 |
| CA2122365C (en) | 1991-11-26 | 2010-05-11 | Brian Froehler | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
| TW393513B (en) | 1991-11-26 | 2000-06-11 | Isis Pharmaceuticals Inc | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| US5644048A (en) | 1992-01-10 | 1997-07-01 | Isis Pharmaceuticals, Inc. | Process for preparing phosphorothioate oligonucleotides |
| DE4234086A1 (de) | 1992-02-05 | 1993-08-12 | Diagen Inst Molekularbio | Verfahren zur bestimmung von in vitro amplifizierten nukleinsaeuresequenzen |
| US5637684A (en) | 1994-02-23 | 1997-06-10 | Isis Pharmaceuticals, Inc. | Phosphoramidate and phosphorothioamidate oligomeric compounds |
| GB9513271D0 (en) | 1995-06-29 | 1995-09-06 | Johnson James G | Stress free fish harvester |
| US5773258A (en) | 1995-08-25 | 1998-06-30 | Roche Molecular Systems, Inc. | Nucleic acid amplification using a reversibly inactivated thermostable enzyme |
| AU726501B2 (en) | 1996-06-04 | 2000-11-09 | University Of Utah Research Foundation | Monitoring hybridization during PCR |
| EP0866071B1 (en) * | 1997-03-20 | 2004-10-20 | F. Hoffmann-La Roche Ag | Modified primers |
| US5849497A (en) | 1997-04-03 | 1998-12-15 | The Research Foundation Of State University Of New York | Specific inhibition of the polymerase chain reaction using a non-extendable oligonucleotide blocker |
| US6228628B1 (en) | 1997-07-09 | 2001-05-08 | Roche Molecular Systems | Mutant chimeric DNA polymerase |
| JP3274396B2 (ja) | 1997-11-07 | 2002-04-15 | 株式会社東芝 | パターン測定方法 |
| CN100432237C (zh) * | 1999-03-19 | 2008-11-12 | 宝生物工程株式会社 | 用于扩增核酸序列的方法 |
| WO2000056746A2 (en) | 1999-03-24 | 2000-09-28 | Exiqon A/S | Improved synthesis of [2.2.1]bicyclo nucleosides |
| AU4682400A (en) | 1999-05-04 | 2000-11-17 | Ortho-Clinical Diagnostics, Inc. | Rapid and efficient capture of dna from sample without using cell lysing reagent |
| EA007414B1 (ru) * | 2000-08-23 | 2006-10-27 | Такара Био Инк. | Химерный олигонуклеотидный праймер для способа амплификации нуклеиновой кислоты; продукт для амплификации нуклеиновой кислоты; зонд для способа детекции нуклеиновой кислоты-мишени; материал с иммобилизованной амплифицированной нуклеиновой кислотой и способ его получения; способ определения нуклеотидной последовательности |
| US6479242B1 (en) * | 2000-10-26 | 2002-11-12 | Cleveland State University | Method for genotyping of single nucleotide polymorphism |
| GB0101397D0 (en) | 2001-01-19 | 2001-03-07 | Amersham Pharm Biotech Uk Ltd | Suppression of non-specific nucleic acid amplication |
| EP1253205A1 (en) | 2001-04-24 | 2002-10-30 | LION Bioscience AG | Method of blocking amplification of selected sequences |
| US7198897B2 (en) * | 2001-12-19 | 2007-04-03 | Brandeis University | Late-PCR |
| US7741467B2 (en) * | 2005-10-05 | 2010-06-22 | Roche Molecular Systems, Inc. | Non-fluorescent energy transfer |
| US7803543B2 (en) | 2007-01-19 | 2010-09-28 | Chang Gung University | Methods and kits for the detection of nucleotide mutations using peptide nucleic acid as both PCR clamp and sensor probe |
| US8071338B2 (en) | 2007-08-08 | 2011-12-06 | Roche Molecular Systems, Inc. | Suppression of amplification using an oligonucleotide and a polymerase significantly lacking 5′-3′ nuclease activity |
| PL2247601T3 (pl) | 2008-07-02 | 2013-09-30 | Avexa Ltd | Tiazopirymidynony i ich zastosowanie |
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- 2010-01-07 CN CN201710109955.4A patent/CN106702000A/zh active Pending
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| WO2010079127A1 (en) | 2010-07-15 |
| EP2385991B1 (en) | 2017-05-17 |
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| US8206929B2 (en) | 2012-06-26 |
| CN102272333A (zh) | 2011-12-07 |
| CA2747068C (en) | 2014-04-08 |
| US20100173311A1 (en) | 2010-07-08 |
| JP5785095B2 (ja) | 2015-09-24 |
| CA2747068A1 (en) | 2010-07-15 |
| CN106702000A (zh) | 2017-05-24 |
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