CN105378107A - 多重甲基化-特异性扩增系统和方法 - Google Patents
多重甲基化-特异性扩增系统和方法 Download PDFInfo
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- 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
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6858—Allele-specific amplification
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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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
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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- 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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/154—Methylation markers
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| US10184154B2 (en) | 2014-09-26 | 2019-01-22 | Mayo Foundation For Medical Education And Research | Detecting cholangiocarcinoma |
| CN107532124B (zh) | 2015-03-27 | 2022-08-09 | 精密科学公司 | 检测食管疾病 |
| WO2016205233A2 (en) * | 2015-06-15 | 2016-12-22 | Cepheid | Integrated purification and measurement of dna methylation and co-measurement of mutations and/or mrna expression levels in an automated reaction cartridge |
| CN108350485A (zh) | 2015-10-30 | 2018-07-31 | 精密科学发展有限责任公司 | 血浆dna的多重扩增检测测定以及分离和检测 |
| WO2017192221A1 (en) | 2016-05-05 | 2017-11-09 | Exact Sciences Corporation | Detection of lung neoplasia by analysis of methylated dna |
| JP7123050B2 (ja) | 2016-12-12 | 2022-08-22 | セファイド | 自動反応カートリッジにおける統合された、ＤＮＡメチル化の精製及び測定並びに変異及び／又はｍＲＮＡ発現レベルの同時測定 |
| CN110475875B (zh) | 2017-01-27 | 2024-06-25 | 精密科学公司 | 通过分析甲基化dna检测结肠瘤形成 |
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| CN114651070A (zh) * | 2019-09-16 | 2022-06-21 | 精密科学公司 | 结构和温度依赖性瓣状核酸内切酶底物 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060110741A1 (en) * | 2002-12-25 | 2006-05-25 | Ryoichi Asai | Nucleic acid methylation detection process using an internal reference sample |
| US20110091882A1 (en) * | 2009-10-02 | 2011-04-21 | Ibis Biosciences, Inc. | Determination of methylation status of polynucleotides |
| CN102424857A (zh) * | 2011-12-30 | 2012-04-25 | 陕西北美基因股份有限公司 | 一种Taqman水解探针以及定量检测MGMT甲基化程度的方法 |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4965188A (en) | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| EP0232967B1 (en) | 1986-01-10 | 1993-04-28 | Amoco Corporation | Competitive homogeneous assay |
| US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
| US5283174A (en) | 1987-09-21 | 1994-02-01 | Gen-Probe, Incorporated | Homogenous protection assay |
| US5130238A (en) | 1988-06-24 | 1992-07-14 | Cangene Corporation | Enhanced nucleic acid amplification process |
| ATE282716T1 (de) | 1989-07-11 | 2004-12-15 | Gen Probe Inc | Verfahren zur amplifikation von nukleinsäuresequenzen |
| CA2020958C (en) | 1989-07-11 | 2005-01-11 | Daniel L. Kacian | Nucleic acid sequence amplification methods |
| US5455166A (en) | 1991-01-31 | 1995-10-03 | Becton, Dickinson And Company | Strand displacement amplification |
| US5270184A (en) | 1991-11-19 | 1993-12-14 | Becton, Dickinson And Company | Nucleic acid target generation |
| SE501439C2 (sv) | 1993-06-22 | 1995-02-13 | Pharmacia Lkb Biotech | Sätt och anordning för analys av polynukleotidsekvenser |
| US5925517A (en) | 1993-11-12 | 1999-07-20 | The Public Health Research Institute Of The City Of New York, Inc. | Detectably labeled dual conformation oligonucleotide probes, assays and kits |
| DE69417918T2 (de) | 1993-11-30 | 2000-01-05 | Mcgill University, Montreal | Dna methyltransferase inhibierung |
| US5714330A (en) | 1994-04-04 | 1998-02-03 | Lynx Therapeutics, Inc. | DNA sequencing by stepwise ligation and cleavage |
| US5648211A (en) | 1994-04-18 | 1997-07-15 | Becton, Dickinson And Company | Strand displacement amplification using thermophilic enzymes |
| US5641658A (en) | 1994-08-03 | 1997-06-24 | Mosaic Technologies, Inc. | Method for performing amplification of nucleic acid with two primers bound to a single solid support |
| WO1996006190A2 (en) | 1994-08-19 | 1996-02-29 | Perkin-Elmer Corporation | Coupled amplification and ligation method |
| US5695934A (en) | 1994-10-13 | 1997-12-09 | Lynx Therapeutics, Inc. | Massively parallel sequencing of sorted polynucleotides |
| JP3189000B2 (ja) | 1994-12-01 | 2001-07-16 | 東ソー株式会社 | 特定核酸配列の検出方法 |
| US5750341A (en) | 1995-04-17 | 1998-05-12 | Lynx Therapeutics, Inc. | DNA sequencing by parallel oligonucleotide extensions |
| US5710029A (en) | 1995-06-07 | 1998-01-20 | Gen-Probe Incorporated | Methods for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product |
| DE69738687D1 (de) | 1996-04-12 | 2008-06-26 | Phri Properties Inc | Sonden, kits und assays |
| US5871917A (en) | 1996-05-31 | 1999-02-16 | North Shore University Hospital Research Corp. | Identification of differentially methylated and mutated nucleic acids |
| US5786146A (en) | 1996-06-03 | 1998-07-28 | The Johns Hopkins University School Of Medicine | Method of detection of methylated nucleic acid using agents which modify unmethylated cytosine and distinguishing modified methylated and non-methylated nucleic acids |
| US6017704A (en) | 1996-06-03 | 2000-01-25 | The Johns Hopkins University School Of Medicine | Method of detection of methylated nucleic acid using agents which modify unmethylated cytosine and distinguishing modified methylated and non-methylated nucleic acids |
| GB9620209D0 (en) | 1996-09-27 | 1996-11-13 | Cemu Bioteknik Ab | Method of sequencing DNA |
| GB9626815D0 (en) | 1996-12-23 | 1997-02-12 | Cemu Bioteknik Ab | Method of sequencing DNA |
| US6969488B2 (en) | 1998-05-22 | 2005-11-29 | Solexa, Inc. | System and apparatus for sequential processing of analytes |
| WO1999019341A1 (en) | 1997-10-10 | 1999-04-22 | President & Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
| US6485944B1 (en) | 1997-10-10 | 2002-11-26 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
| US6511803B1 (en) | 1997-10-10 | 2003-01-28 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
| DE19754482A1 (de) | 1997-11-27 | 1999-07-01 | Epigenomics Gmbh | Verfahren zur Herstellung komplexer DNA-Methylierungs-Fingerabdrücke |
| WO2000001850A2 (en) | 1998-07-02 | 2000-01-13 | Gen-Probe Incorporated | Molecular torches |
| US6787308B2 (en) | 1998-07-30 | 2004-09-07 | Solexa Ltd. | Arrayed biomolecules and their use in sequencing |
| AR021833A1 (es) | 1998-09-30 | 2002-08-07 | Applied Research Systems | Metodos de amplificacion y secuenciacion de acido nucleico |
| US6303305B1 (en) | 1999-03-30 | 2001-10-16 | Roche Diagnostics, Gmbh | Method for quantification of an analyte |
| US6331393B1 (en) * | 1999-05-14 | 2001-12-18 | University Of Southern California | Process for high-throughput DNA methylation analysis |
| US6541205B1 (en) | 1999-05-24 | 2003-04-01 | Tosoh Corporation | Method for assaying nucleic acid |
| US6818395B1 (en) | 1999-06-28 | 2004-11-16 | California Institute Of Technology | Methods and apparatus for analyzing polynucleotide sequences |
| US7501245B2 (en) | 1999-06-28 | 2009-03-10 | Helicos Biosciences Corp. | Methods and apparatuses for analyzing polynucleotide sequences |
| EP1218543A2 (en) | 1999-09-29 | 2002-07-03 | Solexa Ltd. | Polynucleotide sequencing |
| DE19959691A1 (de) * | 1999-12-06 | 2001-08-16 | Epigenomics Ag | Verfahren zur parallelen Detektions des Methylierungszustandes von genomischer DNA |
| DE10010280B4 (de) | 2000-02-25 | 2006-08-10 | Epigenomics Ag | Verfahren zur Detektion von Cytosin-Methylierung in DNA Proben |
| JP2004513619A (ja) | 2000-07-07 | 2004-05-13 | ヴィジゲン バイオテクノロジーズ インコーポレイテッド | リアルタイム配列決定 |
| US6706162B1 (en) | 2000-09-25 | 2004-03-16 | Applera Corporation | High speed, high resolution compositions, methods, and kits for capillary electrophoresis |
| AR031640A1 (es) | 2000-12-08 | 2003-09-24 | Applied Research Systems | Amplificacion isotermica de acidos nucleicos en un soporte solido |
| US20030027135A1 (en) | 2001-03-02 | 2003-02-06 | Ecker David J. | Method for rapid detection and identification of bioagents |
| US7668697B2 (en) | 2006-02-06 | 2010-02-23 | Andrei Volkov | Method for analyzing dynamic detectable events at the single molecule level |
| US7250098B2 (en) | 2001-09-28 | 2007-07-31 | Applera Corporation | Multi-capillary array electrophoresis device |
| DE10215770A1 (de) | 2002-04-10 | 2003-10-30 | Michael Giesing | Verfahren zum Nachweis methylierter und/oder nichtmethylierter Cytosine in Nukleinsäuren, dessen Verwendung sowie entsprechende Analysekits |
| CA2513535C (en) | 2003-01-29 | 2012-06-12 | 454 Corporation | Bead emulsion nucleic acid amplification |
| CA2524572C (en) | 2003-05-01 | 2018-07-10 | Gen-Probe Incorporated | Oligonucleotides comprising a molecular switch having enhanced sensitivity to the presence of a mismatch |
| WO2005042713A2 (en) * | 2003-10-28 | 2005-05-12 | The Johns Hopkins University | Quantitative multiplex methylation-specific pcr |
| US7169560B2 (en) | 2003-11-12 | 2007-01-30 | Helicos Biosciences Corporation | Short cycle methods for sequencing polynucleotides |
| US7696337B2 (en) | 2004-08-27 | 2010-04-13 | Gen-Probe Incorporated | Composition kits and methods for performing amplification reactions |
| JP5774805B2 (ja) * | 2004-11-29 | 2015-09-09 | セクエノム，インコーポレイティド | メチル化ｄｎａを検出する方法、及びキット |
| US7482120B2 (en) | 2005-01-28 | 2009-01-27 | Helicos Biosciences Corporation | Methods and compositions for improving fidelity in a nucleic acid synthesis reaction |
| EP1844162B1 (en) | 2005-02-01 | 2014-10-15 | Applied Biosystems, LLC | Method for identifying a sequence in a polynucleotide |
| WO2007032748A1 (en) | 2005-09-15 | 2007-03-22 | Agency For Science, Technology & Research | Method for detecting dna methylation |
| US7282337B1 (en) | 2006-04-14 | 2007-10-16 | Helicos Biosciences Corporation | Methods for increasing accuracy of nucleic acid sequencing |
| US20080241951A1 (en) | 2006-07-20 | 2008-10-02 | Visigen Biotechnologies, Inc. | Method and apparatus for moving stage detection of single molecular events |
| AU2007334393A1 (en) | 2006-12-14 | 2008-06-26 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
| US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
| US9290803B2 (en) | 2007-04-12 | 2016-03-22 | University Of Southern California | DNA methylation analysis by digital bisulfite genomic sequencing and digital methylight |
| DK2171088T3 (en) | 2007-06-19 | 2016-01-25 | Stratos Genomics Inc | Nucleic acid sequencing in a high yield by expansion |
| US20100137143A1 (en) | 2008-10-22 | 2010-06-03 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
| US20100301398A1 (en) | 2009-05-29 | 2010-12-02 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
-
2014
- 2014-03-13 WO PCT/US2014/025854 patent/WO2014160117A1/en not_active Ceased
- 2014-03-13 CN CN201480027133.6A patent/CN105378107A/zh active Pending
- 2014-03-13 US US14/208,862 patent/US9701999B2/en not_active Expired - Fee Related
- 2014-03-13 JP JP2016501984A patent/JP2016512437A/ja active Pending
- 2014-03-13 EP EP14773416.4A patent/EP2971171A4/en not_active Withdrawn
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2017
- 2017-07-10 US US15/645,754 patent/US20170306395A1/en not_active Abandoned
-
2018
- 2018-12-27 JP JP2018244615A patent/JP2019076100A/ja not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060110741A1 (en) * | 2002-12-25 | 2006-05-25 | Ryoichi Asai | Nucleic acid methylation detection process using an internal reference sample |
| US20110091882A1 (en) * | 2009-10-02 | 2011-04-21 | Ibis Biosciences, Inc. | Determination of methylation status of polynucleotides |
| CN102424857A (zh) * | 2011-12-30 | 2012-04-25 | 陕西北美基因股份有限公司 | 一种Taqman水解探针以及定量检测MGMT甲基化程度的方法 |
Also Published As
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| US20170306395A1 (en) | 2017-10-26 |
| EP2971171A4 (en) | 2016-11-02 |
| US9701999B2 (en) | 2017-07-11 |
| JP2016512437A (ja) | 2016-04-28 |
| JP2019076100A (ja) | 2019-05-23 |
| WO2014160117A1 (en) | 2014-10-02 |
| EP2971171A1 (en) | 2016-01-20 |
| US20140274735A1 (en) | 2014-09-18 |
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