WO1998023733A3 - Thermostable polymerases having altered fidelity - Google Patents

Thermostable polymerases having altered fidelity Download PDF

Info

Publication number
WO1998023733A3
WO1998023733A3 PCT/US1997/021940 US9721940W WO9823733A3 WO 1998023733 A3 WO1998023733 A3 WO 1998023733A3 US 9721940 W US9721940 W US 9721940W WO 9823733 A3 WO9823733 A3 WO 9823733A3
Authority
WO
WIPO (PCT)
Prior art keywords
polymerase
fidelity
provides
thermostable
gene
Prior art date
Application number
PCT/US1997/021940
Other languages
French (fr)
Other versions
WO1998023733A2 (en
Inventor
Lawrence A Loeb
Leroy Hood
Motoshi Suzuki
Original Assignee
Univ Washington
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Washington filed Critical Univ Washington
Publication of WO1998023733A2 publication Critical patent/WO1998023733A2/en
Publication of WO1998023733A3 publication Critical patent/WO1998023733A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1241—Nucleotidyltransferases (2.7.7)
    • C12N9/1252—DNA-directed DNA polymerase (2.7.7.7), i.e. DNA replicase
    • 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
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6858—Allele-specific amplification
    • 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
    • C12Q1/6876—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

Abstract

The present invention provides a method for identifying a thermostable polymerase having altered fidelity. The method consists of generating a random population of polymerase mutants by mutating at least one amino acid residue of a thermostable polymerase and screening the population for one or more active polymerase mutants by genetic selection. For example, the invention provides a method for identifying a thermostable polymerase having altered fidelity by mutating at least one amino acid residue in an active site O-helix of a thermostable polymerase. The invention also provides thermostable polymerases and nucleic acids encoding thermostable polymerases having altered fidelity, for example, high fidelity polymerases and low fidelity polymerases. The invention additionally provides a method for identifying one or more mutations in a gene by amplifying the gene with a high fidelity polymerase. The invention further provides a method for accurately copying repetitive nucleotide sequences using a high fidelity polymerase mutant. The invention also provides a method for diagnosing a genetic disease using a high fidelity polymerase mutant. The invention further provides a method for randomly mutagenizing a gene by amplifying the gene using a low fidelity polymerase mutant.
PCT/US1997/021940 1996-11-27 1997-11-26 Thermostable polymerases having altered fidelity WO1998023733A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3149696P 1996-11-27 1996-11-27
US60/031,496 1996-11-27

Publications (2)

Publication Number Publication Date
WO1998023733A2 WO1998023733A2 (en) 1998-06-04
WO1998023733A3 true WO1998023733A3 (en) 1998-07-16

Family

ID=21859787

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/021940 WO1998023733A2 (en) 1996-11-27 1997-11-26 Thermostable polymerases having altered fidelity

Country Status (2)

Country Link
US (6) US6395524B2 (en)
WO (1) WO1998023733A2 (en)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8841071B2 (en) 2011-06-02 2014-09-23 Raindance Technologies, Inc. Sample multiplexing
US8871444B2 (en) 2004-10-08 2014-10-28 Medical Research Council In vitro evolution in microfluidic systems
US9012390B2 (en) 2006-08-07 2015-04-21 Raindance Technologies, Inc. Fluorocarbon emulsion stabilizing surfactants
US9150852B2 (en) 2011-02-18 2015-10-06 Raindance Technologies, Inc. Compositions and methods for molecular labeling
US9228229B2 (en) 2010-02-12 2016-01-05 Raindance Technologies, Inc. Digital analyte analysis
US9273308B2 (en) 2006-05-11 2016-03-01 Raindance Technologies, Inc. Selection of compartmentalized screening method
US9328344B2 (en) 2006-01-11 2016-05-03 Raindance Technologies, Inc. Microfluidic devices and methods of use in the formation and control of nanoreactors
US9364803B2 (en) 2011-02-11 2016-06-14 Raindance Technologies, Inc. Methods for forming mixed droplets
US9366632B2 (en) 2010-02-12 2016-06-14 Raindance Technologies, Inc. Digital analyte analysis
US9399797B2 (en) 2010-02-12 2016-07-26 Raindance Technologies, Inc. Digital analyte analysis
US9440232B2 (en) 2007-02-06 2016-09-13 Raindance Technologies, Inc. Manipulation of fluids and reactions in microfluidic systems
US9448172B2 (en) 2003-03-31 2016-09-20 Medical Research Council Selection by compartmentalised screening
US9498759B2 (en) 2004-10-12 2016-11-22 President And Fellows Of Harvard College Compartmentalized screening by microfluidic control
US9562897B2 (en) 2010-09-30 2017-02-07 Raindance Technologies, Inc. Sandwich assays in droplets
US9562837B2 (en) 2006-05-11 2017-02-07 Raindance Technologies, Inc. Systems for handling microfludic droplets

Families Citing this family (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6015668A (en) * 1994-09-30 2000-01-18 Life Technologies, Inc. Cloned DNA polymerases from thermotoga and mutants thereof
US5912155A (en) * 1994-09-30 1999-06-15 Life Technologies, Inc. Cloned DNA polymerases from Thermotoga neapolitana
US20030027296A1 (en) * 1995-09-08 2003-02-06 Deb K. Chatterjee Cloned dna polymerases from thermotoga maritima and mutants thereof
EP1007730A4 (en) 1996-08-30 2004-04-28 Invitrogen Corp METHODS FOR IDENTIFICATION AND ISOLATION OF SPECIFIC NUCLEOTIDE SEQUENCES IN cDNA AND GENOMIC DNA
US6395524B2 (en) * 1996-11-27 2002-05-28 University Of Washington Thermostable polymerases having altered fidelity and method of identifying and using same
US6306588B1 (en) 1997-02-07 2001-10-23 Invitrogen Corporation Polymerases for analyzing or typing polymorphic nucleic acid fragments and uses thereof
CA2792122C (en) 1997-07-07 2015-09-08 Medical Research Council In vitro sorting method
CA2302393A1 (en) * 1997-08-29 1999-03-04 Life Technologies, Inc. High fidelity polymerases and uses thereof
US20050287592A1 (en) 2000-08-29 2005-12-29 Yeda Research And Development Co. Ltd. Template-dependent nucleic acid polymerization using oligonucleotide triphosphates building blocks
MXPA02002163A (en) 1999-09-01 2004-04-21 Yeda Res & Dev Template-dependent nucleic acid polymerization using oligonucleotide triphosphates building blocks.
FR2799473A1 (en) * 1999-10-12 2001-04-13 Inst Necker DNA POLYMERASE HAVING MUTASE ACTIVITY AND USE THEREOF
US6329178B1 (en) 2000-01-14 2001-12-11 University Of Washington DNA polymerase mutant having one or more mutations in the active site
US7056716B2 (en) * 2000-03-15 2006-06-06 Invitrogen Corporation High fidelity reverse transcriptases and uses thereof
AU2007201277B2 (en) * 2000-05-24 2011-10-13 Third Wave Technologies, Inc. Detection of RNA
CN1430670A (en) * 2000-05-26 2003-07-16 茵维特罗根公司 Thermostable reverse transcriptases and uses thereof
US9771565B2 (en) 2000-05-26 2017-09-26 Life Technologies Corporation Thermostable reverse transcriptases and uses thereof
US6214557B1 (en) * 2000-06-06 2001-04-10 Washington University Cold sensitive mutant DNA polymerases
US7198924B2 (en) 2000-12-11 2007-04-03 Invitrogen Corporation Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites
GB0022458D0 (en) * 2000-09-13 2000-11-01 Medical Res Council Directed evolution method
FR2816319B1 (en) * 2000-11-08 2004-09-03 Millegen USE OF DNA MUTAGEN POLYMERASE FOR THE CREATION OF RANDOM MUTATIONS
GB0127564D0 (en) 2001-11-16 2002-01-09 Medical Res Council Emulsion compositions
WO2004024749A2 (en) 2002-09-13 2004-03-25 Invitrogen Corporation Thermostable reverse transcriptases and uses thereof
AU2004254552B2 (en) 2003-01-29 2008-04-24 454 Life Sciences Corporation Methods of amplifying and sequencing nucleic acids
US20060078893A1 (en) 2004-10-12 2006-04-13 Medical Research Council Compartmentalised combinatorial chemistry by microfluidic control
GB0307428D0 (en) 2003-03-31 2003-05-07 Medical Res Council Compartmentalised combinatorial chemistry
EP2918595B1 (en) 2003-07-05 2019-12-11 The Johns-Hopkins University Method and compositions for detection and enumeration of genetic variations
GB0325653D0 (en) 2003-11-03 2003-12-10 Medical Res Council CST emulsions
EP1697534B1 (en) 2003-12-01 2010-06-02 Life Technologies Corporation Nucleic acid molecules containing recombination sites and methods of using the same
DE102004005885A1 (en) * 2004-02-05 2005-10-13 Rheinische Friedrich-Wilhelms-Universität Bonn Mutated DNA polymerases with increased mismatch discrimination
US7417133B2 (en) 2004-02-27 2008-08-26 Institut Pasteur Methods for obtaining thermostable enzymes, DNA polymerase I variants from Thermus aquaticus having new catalytic activities, methods for obtaining the same, and applications of the same
GB0420500D0 (en) * 2004-09-15 2004-10-20 Univ Newcastle DNA polymerases
US20070048748A1 (en) * 2004-09-24 2007-03-01 Li-Cor, Inc. Mutant polymerases for sequencing and genotyping
WO2008130623A1 (en) 2007-04-19 2008-10-30 Brandeis University Manipulation of fluids, fluid components and reactions in microfluidic systems
US7939259B2 (en) 2007-06-19 2011-05-10 Stratos Genomics, Inc. High throughput nucleic acid sequencing by expansion
EP2455463A3 (en) * 2007-07-12 2012-09-05 New England Biolabs, Inc. High fidelity restriction endonucleases
GB0806562D0 (en) 2008-04-10 2008-05-14 Fermentas Uab Production of nucleic acid
EP4047367A1 (en) 2008-07-18 2022-08-24 Bio-Rad Laboratories, Inc. Method for detecting target analytes with droplet libraries
WO2010088557A1 (en) 2009-01-29 2010-08-05 Stratos Genomics Inc. High throughput nucleic acid sequencing by expansion and related methods
EP3415235A1 (en) 2009-03-23 2018-12-19 Raindance Technologies Inc. Manipulation of microfluidic droplets
WO2011042564A1 (en) 2009-10-09 2011-04-14 Universite De Strasbourg Labelled silica-based nanomaterial with enhanced properties and uses thereof
EP2517025B1 (en) 2009-12-23 2019-11-27 Bio-Rad Laboratories, Inc. Methods for reducing the exchange of molecules between droplets
US10351905B2 (en) 2010-02-12 2019-07-16 Bio-Rad Laboratories, Inc. Digital analyte analysis
WO2011157435A1 (en) 2010-06-18 2011-12-22 Roche Diagnostics Gmbh Dna polymerases with increased 3'-mismatch discrimination
EP2582804B1 (en) 2010-06-18 2015-02-25 Roche Diagnostics GmbH Dna polymerases with increased 3'-mismatch discrimination
CA2802304C (en) 2010-06-18 2016-01-12 F.Hoffman-La Roche Ag Dna polymerases with increased 3'-mismatch discrimination
WO2012110060A1 (en) 2011-02-15 2012-08-23 Roche Diagnostics Gmbh Dna polymerases with increased 3'-mismatch discrimination
WO2012110061A1 (en) 2011-02-15 2012-08-23 Roche Diagnostics Gmbh Dna polymerases with increased 3'-mismatch discrimination
WO2012139748A1 (en) * 2011-04-11 2012-10-18 Roche Diagnostics Gmbh Dna polymerases with improved activity
EP3709018A1 (en) 2011-06-02 2020-09-16 Bio-Rad Laboratories, Inc. Microfluidic apparatus for identifying components of a chemical reaction
JP5830286B2 (en) * 2011-07-12 2015-12-09 アークレイ株式会社 Nucleic acid amplification detection method and kit
US8658430B2 (en) 2011-07-20 2014-02-25 Raindance Technologies, Inc. Manipulating droplet size
GB201113430D0 (en) 2011-08-03 2011-09-21 Fermentas Uab DNA polymerases
EP3293274B1 (en) 2011-08-10 2020-04-01 Life Technologies Corporation Polymerase compositions
US11208636B2 (en) 2011-08-10 2021-12-28 Life Technologies Corporation Polymerase compositions, methods of making and using same
ES2683707T3 (en) 2012-05-02 2018-09-27 Ibis Biosciences, Inc. DNA sequencing
EP2844774B1 (en) 2012-05-02 2018-07-18 Ibis Biosciences, Inc. Dna sequencing
EP3438285B1 (en) 2012-05-02 2020-10-14 Ibis Biosciences, Inc. Dna sequencing
CN103509767B (en) * 2012-06-27 2016-08-03 菲鹏生物股份有限公司 A kind of Mutant Taq enzyme and preparation method thereof
US9212392B2 (en) 2012-09-25 2015-12-15 Exact Sciences Corporation Normalization of polymerase activity
CN103266103B (en) * 2012-11-08 2016-08-31 天津精耐特基因生物技术有限公司 For expanding the method for ribonucleic acid and analyzing RNA or the method for DNA profiling in the method
EP2971154A4 (en) 2013-03-14 2017-03-01 Ibis Biosciences, Inc. Nucleic acid control panels
US10428379B2 (en) 2013-03-15 2019-10-01 Ibis Biosciences, Inc. Nucleotide analogs for sequencing
EP3036359B1 (en) 2013-08-19 2019-10-23 Abbott Molecular Inc. Next-generation sequencing libraries
WO2015026845A2 (en) 2013-08-19 2015-02-26 Abbott Molecular Inc. Nucleotide analogs
US11901041B2 (en) 2013-10-04 2024-02-13 Bio-Rad Laboratories, Inc. Digital analysis of nucleic acid modification
US9944977B2 (en) 2013-12-12 2018-04-17 Raindance Technologies, Inc. Distinguishing rare variations in a nucleic acid sequence from a sample
US11193176B2 (en) 2013-12-31 2021-12-07 Bio-Rad Laboratories, Inc. Method for detecting and quantifying latent retroviral RNA species
WO2015112767A2 (en) 2014-01-22 2015-07-30 Life Technologies Corporation Novel reverse transcriptases for use in high temperature nucleic acid synthesis
EP3218471A1 (en) 2014-11-14 2017-09-20 Illumina, Inc. Polymerases
CN107208074B (en) 2014-12-16 2021-06-15 生命技术公司 Polymerase compositions and methods of making and using the same
CN105039278B (en) * 2015-06-17 2018-09-11 菲鹏生物股份有限公司 Saltant type Taq archaeal dna polymerases and its preparation method and application
US10647981B1 (en) 2015-09-08 2020-05-12 Bio-Rad Laboratories, Inc. Nucleic acid library generation methods and compositions
EP3998353A1 (en) 2015-10-30 2022-05-18 Exact Sciences Corporation Multiplex amplification detection assay and isolation and detection of dna from plasma
KR102436270B1 (en) 2016-05-05 2022-08-25 이그젝트 싸이언스 디블롭먼트 컴패니, 엘엘씨 Detection of lung tumors by methylated DNA analysis
EP4253565A2 (en) 2017-01-24 2023-10-04 Vastogen, Inc. Methods for constructing copies of nucleic acid molecules
US11118228B2 (en) 2017-01-27 2021-09-14 Exact Sciences Development Company, Llc Detection of colon neoplasia by analysis of methylated DNA
US10648025B2 (en) 2017-12-13 2020-05-12 Exact Sciences Development Company, Llc Multiplex amplification detection assay II
WO2019122200A1 (en) 2017-12-22 2019-06-27 Thermo Fisher Scientific Baltics Uab Polymerase chain reaction composition comprising amines
WO2020142255A1 (en) 2018-12-31 2020-07-09 Abbott Molecular Inc. Improved amplification of nucleic acids
CN115161302B (en) * 2021-03-25 2023-08-29 山东大学 High-specificity Taq DNA polymerase variant and obtaining method and application thereof
US20220403450A1 (en) 2021-06-03 2022-12-22 Illumina Software, Inc. Systems and methods for sequencing nucleotides using two optical channels
AU2022303381A1 (en) 2021-07-01 2024-01-18 Illumina, Inc. Device having horizontal nanochannel for nanopore sequencing
WO2023034079A1 (en) 2021-09-01 2023-03-09 Illumina Software, Inc. Amplitude modulation for accelerated base calling
CA3223744A1 (en) 2021-09-22 2023-03-30 Jeffrey Mandell Sequencing polynucleotides using nanopores
US20230112203A1 (en) 2021-09-30 2023-04-13 Illumina, Inc. Isolation of cells in a nanopore sensor array
WO2023107622A1 (en) 2021-12-10 2023-06-15 Illumina, Inc. Parallel sample and index sequencing
WO2023175024A1 (en) 2022-03-15 2023-09-21 Illumina, Inc. Paired-end sequencing
US20230357307A1 (en) 2022-05-04 2023-11-09 Illumina, Inc. Cleavable cyclic loop nucleotides for nanopore sequencing

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991002090A1 (en) * 1989-08-03 1991-02-21 Promega Corporation Modified taq dna polymerase
EP0416801A2 (en) * 1989-09-07 1991-03-13 Zeneca Limited Method for the detection of cystic fibrosis alleles
WO1995014782A2 (en) * 1993-11-23 1995-06-01 State Of Oregon Acting By And Through The Oregon State Board Of Higher Education On Behalf Of The Oregon Health Sciences University A modified thermo resistant dna polymerase
WO1996010640A1 (en) * 1994-09-30 1996-04-11 Life Technologies, Inc. Cloned dna polymerases from thermotoga neapolitana and mutants thereof
EP0727496A2 (en) * 1994-10-17 1996-08-21 THE PRESIDENT & FELLOWS OF HARVARD COLLEGE DNA polymerases
WO1996034980A1 (en) * 1995-05-03 1996-11-07 Rhone-Poulenc Rorer S.A. Method for diagnosing schizophrenia

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6074818A (en) 1990-08-24 2000-06-13 The University Of Tennessee Research Corporation Fingerprinting of nucleic acids, products and methods
US6015668A (en) 1994-09-30 2000-01-18 Life Technologies, Inc. Cloned DNA polymerases from thermotoga and mutants thereof
EP0655506B1 (en) 1994-10-17 1996-09-18 President And Fellows Of Harvard College DNA polymerases having modified nucleotide binding site for DNA sequencing
US6077664A (en) 1995-06-07 2000-06-20 Promega Corporation Thermophilic DNA polymerases from Thermotoga neapolitana
GB2302590A (en) 1995-06-23 1997-01-22 Scie Plas Limited Low voltage electrophoresis unit with separable battery pack
US5948614A (en) 1995-09-08 1999-09-07 Life Technologies, Inc. Cloned DNA polymerases from thermotoga maritima and mutants thereof
EP0910664A1 (en) 1996-04-15 1999-04-28 University Of Southern California Synthesis of fluorophore-labeled dna
CZ293215B6 (en) 1996-08-06 2004-03-17 F. Hoffmann-La Roche Ag Enzyme of thermally stable DNA polymerase, process of its preparation and a pharmaceutical composition and a kit containing thereof
US6395524B2 (en) * 1996-11-27 2002-05-28 University Of Washington Thermostable polymerases having altered fidelity and method of identifying and using same
US5976842A (en) 1997-10-30 1999-11-02 Clontech Laboratories, Inc. Methods and compositions for use in high fidelity polymerase chain reaction

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991002090A1 (en) * 1989-08-03 1991-02-21 Promega Corporation Modified taq dna polymerase
EP0416801A2 (en) * 1989-09-07 1991-03-13 Zeneca Limited Method for the detection of cystic fibrosis alleles
WO1995014782A2 (en) * 1993-11-23 1995-06-01 State Of Oregon Acting By And Through The Oregon State Board Of Higher Education On Behalf Of The Oregon Health Sciences University A modified thermo resistant dna polymerase
WO1996010640A1 (en) * 1994-09-30 1996-04-11 Life Technologies, Inc. Cloned dna polymerases from thermotoga neapolitana and mutants thereof
EP0727496A2 (en) * 1994-10-17 1996-08-21 THE PRESIDENT & FELLOWS OF HARVARD COLLEGE DNA polymerases
WO1996034980A1 (en) * 1995-05-03 1996-11-07 Rhone-Poulenc Rorer S.A. Method for diagnosing schizophrenia

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
L.A. LOEB: "Microsatellite instability: Marker of a mutator phenotype in cancer", CANCER RESEARCH, vol. 54, 1994, PHILADELPHIA, PA, US, pages 5059 - 5063, XP002064237 *
M. SUZUKI ET AL.,: "Low fidelity mutants in the O-helix of Thermus aquaticus DNA polymerase I", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 17, 25 April 1997 (1997-04-25), BETHESDA, MD, US, pages 11228 - 11235, XP002062866 *
M. SUZUKI ET AL.,: "Random mutagenesis of Thermus aquaticus DNA polymerase I: Concordance of immutable sites in vivo with the crystal structure", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 93, 1 September 1996 (1996-09-01), WASHINGTON, DC, US, pages 9670 - 9675, XP002062865 *
S.TABOR AND C.C. RICHARDSON: "A single residue in DNA polymerases of the Escherichia coli DNA polymerase I family is critical for distinguishing between deoxy and dideoxyribonucleotides", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 92, 1995, WASHINGTON, DC, US, pages 6339 - 6343, XP000606203 *
T.G. NEWCOMB ET AL.,: "High fidelity Taq polymerases for mutation detection", FASEB JOURNAL, vol. 11, no. 9, 24 August 1997 (1997-08-24), BETHESDA,MD, US, pages A1249, XP002062867 *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9448172B2 (en) 2003-03-31 2016-09-20 Medical Research Council Selection by compartmentalised screening
US9186643B2 (en) 2004-10-08 2015-11-17 Medical Research Council In vitro evolution in microfluidic systems
US8871444B2 (en) 2004-10-08 2014-10-28 Medical Research Council In vitro evolution in microfluidic systems
US9498759B2 (en) 2004-10-12 2016-11-22 President And Fellows Of Harvard College Compartmentalized screening by microfluidic control
US9328344B2 (en) 2006-01-11 2016-05-03 Raindance Technologies, Inc. Microfluidic devices and methods of use in the formation and control of nanoreactors
US9534216B2 (en) 2006-01-11 2017-01-03 Raindance Technologies, Inc. Microfluidic devices and methods of use in the formation and control of nanoreactors
US9273308B2 (en) 2006-05-11 2016-03-01 Raindance Technologies, Inc. Selection of compartmentalized screening method
US9562837B2 (en) 2006-05-11 2017-02-07 Raindance Technologies, Inc. Systems for handling microfludic droplets
US9012390B2 (en) 2006-08-07 2015-04-21 Raindance Technologies, Inc. Fluorocarbon emulsion stabilizing surfactants
US9498761B2 (en) 2006-08-07 2016-11-22 Raindance Technologies, Inc. Fluorocarbon emulsion stabilizing surfactants
US9440232B2 (en) 2007-02-06 2016-09-13 Raindance Technologies, Inc. Manipulation of fluids and reactions in microfluidic systems
US9228229B2 (en) 2010-02-12 2016-01-05 Raindance Technologies, Inc. Digital analyte analysis
US9399797B2 (en) 2010-02-12 2016-07-26 Raindance Technologies, Inc. Digital analyte analysis
US9366632B2 (en) 2010-02-12 2016-06-14 Raindance Technologies, Inc. Digital analyte analysis
US9562897B2 (en) 2010-09-30 2017-02-07 Raindance Technologies, Inc. Sandwich assays in droplets
US9364803B2 (en) 2011-02-11 2016-06-14 Raindance Technologies, Inc. Methods for forming mixed droplets
US9150852B2 (en) 2011-02-18 2015-10-06 Raindance Technologies, Inc. Compositions and methods for molecular labeling
US8841071B2 (en) 2011-06-02 2014-09-23 Raindance Technologies, Inc. Sample multiplexing

Also Published As

Publication number Publication date
US20110143356A1 (en) 2011-06-16
US6395524B2 (en) 2002-05-28
US20140051072A1 (en) 2014-02-20
US8420325B2 (en) 2013-04-16
US20020192663A1 (en) 2002-12-19
US6982144B2 (en) 2006-01-03
US20090004656A1 (en) 2009-01-01
US20050196800A1 (en) 2005-09-08
US7312059B2 (en) 2007-12-25
WO1998023733A2 (en) 1998-06-04
US20010012613A1 (en) 2001-08-09

Similar Documents

Publication Publication Date Title
WO1998023733A3 (en) Thermostable polymerases having altered fidelity
Alberts et al. Recent excitement in the DNA replication problem
HUT77576A (en) Enzymatic dna molecules
AU3365095A (en) High throughput screening method for sequences or genetic alterations in nucleic acids
CA2188660A1 (en) Detection of mutation by resolvase cleavage
EP0910664A1 (en) Synthesis of fluorophore-labeled dna
AU1367897A (en) A method for in vivo production of a mutant library in cells
CA2167838A1 (en) Methods for Enhancing Nucleic Acid Amplification
DE69636866D1 (en) Reverse "two-hybrid"-systeme
CA2240346A1 (en) Methods for the detection and removal of mutant sequences that arise during enzymatic amplification using mismatch repair systems
SG173213A1 (en) Identification of genes
Sapolsky et al. Mapping genomic library clones using oligonucleotide arrays
WO2001031055A3 (en) Method and kit for the screening and/or the quantification of multiple homologous nucleic acid sequences on arrays
Lehtovaara et al. A new method for random mutagenesis of complete genes: enzymatic generation of mutant libraries in vitro
PL346126A1 (en) Novel methods for the identification of ligand and target biomolecules
WO2003048309A3 (en) Thermus thermophilus nucleic acid polymerases
EP0763599A3 (en) DNA encoding thermostable pyrophosphatase
EP1251182A3 (en) Method of amplifying and detecting target nucleic acid sequence by using thermostable enzymes
CA2430582A1 (en) A method for in vitro molecular evolution of protein function
Negishi et al. The mechanism of mutation induction by a hydrogen bond ambivalent, bicyclic N 4-oxy-2′-deoxycytidine in Escherichia coli
EP1209612A3 (en) Methods and computer software products for predicting nucleic acid hybridization affinity
Uemura et al. supN ochre suppressor gene in Escherichia coli codes for tRNALys
Andrews et al. Selection strategy for site-directed mutagenesis based on altered β-lactamase specificity
AU2003252350A1 (en) Method of detecting base mutation
Dalbadie-McFarland et al. In Vitro Mutagenesis: Relationships in Proteins Powerful New Techniques for Studying Structure-Function Relationships in Proteins

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): CA JP

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase