CA2196898C - Methods for measuring telomere length - Google Patents
Methods for measuring telomere length Download PDFInfo
- Publication number
- CA2196898C CA2196898C CA002196898A CA2196898A CA2196898C CA 2196898 C CA2196898 C CA 2196898C CA 002196898 A CA002196898 A CA 002196898A CA 2196898 A CA2196898 A CA 2196898A CA 2196898 C CA2196898 C CA 2196898C
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- telomere
- dna
- probe
- cells
- telomere length
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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
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
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- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
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| PCT/US1996/010035 WO1996041016A1 (en) | 1995-06-07 | 1996-06-06 | Methods for measuring telomere length |
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| CA2196898A1 CA2196898A1 (en) | 1996-12-19 |
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| ATE362546T1 (de) | 1995-10-12 | 2007-06-15 | Lansdorp Peter M | Verfahren zum nachweis von mehrfachkopien einer wiederholungssequenz in einem nukleinsäuremolekül |
| WO1998000537A1 (en) | 1996-07-01 | 1998-01-08 | Universite De Sherbrooke | Composition and methods for modulating the length of telomeres |
| FI990655A7 (fi) | 1996-10-01 | 1999-06-01 | Geron Corp | Ihmistelomeraasin katalyyttinen alayksikkö |
| US6117634A (en) * | 1997-03-05 | 2000-09-12 | The Reagents Of The University Of Michigan | Nucleic acid sequencing and mapping |
| US6197557B1 (en) * | 1997-03-05 | 2001-03-06 | The Regents Of The University Of Michigan | Compositions and methods for analysis of nucleic acids |
| US5871926A (en) * | 1997-04-21 | 1999-02-16 | The University Of New Mexico | Sensitive method for measurement of telomeric DNA content in human tissues |
| JP4013333B2 (ja) * | 1998-06-05 | 2007-11-28 | 株式会社Ｂ＆Ｃラボラトリーズ | 皮膚の老化度の測定方法および測定用キット |
| US7981599B1 (en) | 1998-07-31 | 2011-07-19 | Boston Probes, Inc. | Non-nucleic acid probes, probe sets, methods and kits pertaining to the detection of individual human chromosomes X, Y, 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 16, 17, 18 and 20 as 13/21 as a pair |
| US7270958B2 (en) | 1998-09-10 | 2007-09-18 | The Regents Of The University Of Michigan | Compositions and methods for analysis of nucleic acids |
| US6280947B1 (en) | 1999-08-11 | 2001-08-28 | Exact Sciences Corporation | Methods for detecting nucleotide insertion or deletion using primer extension |
| US6503718B2 (en) | 1999-01-10 | 2003-01-07 | Exact Sciences Corporation | Methods for detecting mutations using primer extension for detecting disease |
| US8114850B2 (en) * | 1999-04-08 | 2012-02-14 | Advanced Cancer Therapeutics, Llc | Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin |
| US7314926B1 (en) | 1999-04-08 | 2008-01-01 | Antisoma Research Limited | Antiproliferative activity of g-rich oligonucleotides and method of using same to bind to nucleolin |
| US20080318889A1 (en) * | 1999-04-08 | 2008-12-25 | Antisoma Research Limited | Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin |
| US7960540B2 (en) * | 1999-04-08 | 2011-06-14 | Advanced Cancer Therapeutics, Llc | Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin |
| US20080318890A1 (en) * | 1999-04-08 | 2008-12-25 | Antisoma Research Limited | Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin |
| WO2000074667A2 (en) * | 1999-06-04 | 2000-12-14 | Au Jessie L S | Compositions active in telomere damage comprising a taxane and telomerase inhibitor |
| US6995145B1 (en) | 1999-06-04 | 2006-02-07 | Au Jessie L-S | Methods and compositions for modulating drug activity through telomere damage |
| GB0005281D0 (en) * | 2000-03-07 | 2000-04-26 | Secr Defence | Analytical method |
| GB0009784D0 (en) * | 2000-04-20 | 2000-06-07 | Simeg Limited | Methods for clinical diagnosis |
| WO2003000927A2 (en) * | 2001-06-23 | 2003-01-03 | University Of Wales College Of Medicine | Method for the determination of telomere length |
| US20030124549A1 (en) * | 2001-10-11 | 2003-07-03 | Xerox Corporation | Devices and methods for detecting genetic sequences |
| DE10161829B4 (de) * | 2001-12-15 | 2006-02-16 | Peter Lahnert | Neue Methode zur Bestimmung der Telomerlänge und ihre Verwendung zur Abschätzung des Lebensalters |
| JP4515767B2 (ja) * | 2002-01-31 | 2010-08-04 | ユニバーシティ・オブ・ユタ | 非標的核酸依存性増幅の低減：反復核酸配列の増幅 |
| WO2003071252A2 (en) | 2002-02-15 | 2003-08-28 | Exact Sciences Corporation | Methods for analysis of molecular events |
| US6916621B2 (en) | 2002-03-27 | 2005-07-12 | Spectral Genomics, Inc. | Methods for array-based comparitive binding assays |
| US20040234961A1 (en) * | 2002-04-22 | 2004-11-25 | Fordyce Colleen A. | Telomere length determination and applications |
| GB0214842D0 (en) * | 2002-06-27 | 2002-08-07 | Simeg Ltd | Diagnostic method |
| AU2003284234A1 (en) * | 2002-10-16 | 2004-05-04 | Women And Infants Hospital Of Rhode Island, Inc. | Methods of assessing the risk of reproductive failure by measuring telomere length |
| KR100479264B1 (ko) * | 2002-11-01 | 2005-03-28 | 한국전자통신연구원 | 주기적 가열과 냉각을 통한 혼성화 방법 및 이를 사용하는폴리뉴클레오타이드 검출 장치 |
| EP2474822A1 (en) | 2003-01-24 | 2012-07-11 | University of Utah | Methods of predicting mortality risk by determining telomere length |
| WO2004106490A2 (en) * | 2003-05-28 | 2004-12-09 | The Johns Hopkins University | NOVEL METHODS FOR FINDING MUTATIONS CAUSED BY THE INSERTION OF REPETEAD DNAs |
| US20080108057A1 (en) * | 2004-06-22 | 2008-05-08 | Griffith Jeffrey K | Allelic imbalance in the diagnosis and prognosis of cancer |
| WO2006026654A2 (en) | 2004-08-27 | 2006-03-09 | Exact Sciences Corporation | Method for detecting a recombinant event |
| US9109256B2 (en) | 2004-10-27 | 2015-08-18 | Esoterix Genetic Laboratories, Llc | Method for monitoring disease progression or recurrence |
| US9777314B2 (en) | 2005-04-21 | 2017-10-03 | Esoterix Genetic Laboratories, Llc | Analysis of heterogeneous nucleic acid samples |
| US20100291560A1 (en) * | 2007-03-27 | 2010-11-18 | The Johns Hopkins University | Methods and compositions for diagnosis and treatment of dyskeratosis congenita and related disorders |
| EP2191013A1 (en) * | 2007-08-10 | 2010-06-02 | Tina Holding APS | Method for estimating telomere length |
| US20090131351A1 (en) * | 2007-11-16 | 2009-05-21 | Antisoma Research Limited | Methods, compositions, and kits for modulating tumor cell proliferation |
| WO2009138117A1 (en) * | 2008-05-12 | 2009-11-19 | Fundación Centro Nacional De Investigaciones Oncológicas Carlos Iii | Methods and reagents for the determination of telomere length in a semi-automatic manner of every single cell in a immobilized cell population |
| US8084203B2 (en) | 2008-05-12 | 2011-12-27 | Fundacion Centro Nacional De Investigaciones Oncologicas Carlos Iii | Methods for the determination of telomere length in a semi-automatic manner of every single cell in a immobilized cell population |
| US20090298709A1 (en) * | 2008-05-28 | 2009-12-03 | Affymetrix, Inc. | Assays for determining telomere length and repeated sequence copy number |
| PT3029154T (pt) | 2008-10-17 | 2017-12-06 | Geron Corp | Método para identificação de sensibilidade de um paciente à terapia de inibição da telomerase |
| CA2748265C (en) | 2008-12-22 | 2018-04-03 | University Of Utah Research Foundation | Monochrome multiplex quantitative pcr |
| CN102791877A (zh) * | 2009-11-06 | 2012-11-21 | 酶学有限公司 | 使用双链核酸复合物与耐热聚合酶用于合成脱氧核糖核苷酸链的组合物和方法 |
| US20130217585A1 (en) * | 2010-08-25 | 2013-08-22 | The Trustees Of The University Of Columbia In The City Of New York | Quantitative Total Definition of Biologically Active Sequence Elements |
| US20120196284A1 (en) * | 2010-12-16 | 2012-08-02 | University Of Medicine And Dentistry Of New Jersey | Method of Measuring Telomere Length |
| RU2508407C9 (ru) * | 2012-10-10 | 2014-05-20 | Елена Андреевна Чирясова | Способ количественной оценки терминальных нуклеотидов g-цепи теломерной днк человека с помощью полимеразной цепной реакции и дуплекс-специфического анализа, наборы синтетических олигонуклеотидных праймеров и зондов для осуществления этого способа |
| US9200327B2 (en) | 2012-11-30 | 2015-12-01 | Geron Corporation | Diagnostic markers for treating cell proliferative disorders with telomerase inhibitors |
| CA3176825A1 (en) | 2013-03-15 | 2014-09-18 | Elixirgen Therapeutics, Inc. | Methods of using zscan4 for treating a disease or condition associated with a karyotype abnormality |
| EP2999800B1 (en) | 2013-05-22 | 2019-09-25 | Telomere Diagnostics Inc. | Measures of short telomere abundance |
| JP2016537345A (ja) | 2013-11-13 | 2016-12-01 | ノバルティス アーゲー | 免疫応答を増強するためのｍＴＯＲ阻害剤 |
| EP3087101B1 (en) | 2013-12-20 | 2024-06-05 | Novartis AG | Regulatable chimeric antigen receptor |
| JP2017528433A (ja) | 2014-07-21 | 2017-09-28 | ノバルティス アーゲー | 低い免疫増強用量のｍＴＯＲ阻害剤とＣＡＲの組み合わせ |
| WO2016014553A1 (en) | 2014-07-21 | 2016-01-28 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
| KR102255304B1 (ko) | 2014-09-26 | 2021-05-24 | 삼성전자주식회사 | 텔로미어 증폭 방법 |
| GB201418144D0 (en) * | 2014-10-14 | 2014-11-26 | Univ Cardiff | High throughput sequencing |
| CA2971169A1 (en) | 2014-12-30 | 2016-07-07 | Telomere Diagnostics, Inc. | Multiplex quantitative pcr |
| WO2016149612A2 (en) * | 2015-03-19 | 2016-09-22 | The Johns Hopkins University | Assay for telomere length regulators |
| CN107847491A (zh) | 2015-05-20 | 2018-03-27 | 诺华公司 | 依维莫司(everolimus)与达托里昔布(dactolisib)的医药组合 |
| CN110114070A (zh) | 2016-11-23 | 2019-08-09 | 诺华公司 | 使用依维莫司(everolimus)、达托里昔布(dactolisib)或二者增强免疫反应的方法 |
| CN106755429A (zh) * | 2016-12-27 | 2017-05-31 | 上海三誉生物科技有限公司 | 一种精确测量人群端粒长度的方法 |
| IL303660A (en) | 2017-05-02 | 2023-08-01 | Revolution Medicines Inc | Rapamycin analogs as mtor inhibitors |
| EP3676609A4 (en) * | 2017-09-01 | 2021-06-02 | Children's Medical Research Institute | TELOMERES EVALUATION PROCESS |
| US10098922B1 (en) | 2017-11-30 | 2018-10-16 | Optigenex, Inc. | Increasing telomere length in a cell |
| WO2019157516A1 (en) | 2018-02-12 | 2019-08-15 | resTORbio, Inc. | Combination therapies |
| CA3098692A1 (en) | 2018-05-01 | 2019-11-07 | Revolution Medicines, Inc. | C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors |
| WO2019212991A1 (en) | 2018-05-01 | 2019-11-07 | Revolution Medicines, Inc. | C26-linked rapamycin analogs as mtor inhibitors |
| EP3674418A1 (en) * | 2018-12-26 | 2020-07-01 | Life Length S.L. | Method for measuring telomere associated variables and uses thereof for the diagnosis and/or prognosis of telomeric-associated diseases |
| WO2021025935A1 (en) * | 2019-08-02 | 2021-02-11 | Georgetown University | Dna-fish method for measurement of telomere length |
| AU2023275778A1 (en) | 2022-05-25 | 2024-12-12 | Revolution Medicines, Inc. | Methods of treating cancer with an mtor inhibitor |
| CN117230169B (zh) * | 2023-11-13 | 2024-02-13 | 元码基因科技（北京）股份有限公司 | 用于长片段端粒序列测序的接头、预文库及其构建方法 |
| CN117248003B (zh) * | 2023-11-13 | 2024-04-12 | 元码基因科技（北京）股份有限公司 | 用于完整端粒扩增子测序的组合物、预文库及其构建方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4737454A (en) * | 1983-07-14 | 1988-04-12 | Molecular Diagnostics, Inc. | Fast photochemical method of labelling nucleic acids for detection purposes in hybridization assays |
| US5629154A (en) * | 1993-11-12 | 1997-05-13 | Geron Corporation | Telomerase activity assays |
| US5489508A (en) * | 1992-05-13 | 1996-02-06 | University Of Texas System Board Of Regents | Therapy and diagnosis of conditions related to telomere length and/or telomerase activity |
| IL107150A0 (en) * | 1992-09-29 | 1993-12-28 | Isis Pharmaceuticals Inc | Oligonucleotides having a conserved g4 core sequence |
| WO1995013382A1 (en) * | 1993-11-12 | 1995-05-18 | Geron Corporation | Therapy and diagnosis of conditions related to telomere length and/or telomerase activity |
| EP0787203A1 (en) * | 1994-10-21 | 1997-08-06 | Zeneca Limited | Method for characterising variability in telomere dna by pcr |
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1995
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- 1996-06-06 JP JP50217097A patent/JP4294092B2/ja not_active Expired - Lifetime
- 1996-06-06 CA CA002196898A patent/CA2196898C/en not_active Expired - Lifetime
- 1996-06-06 EP EP96921515A patent/EP0774014A4/en not_active Withdrawn
- 1996-06-06 AU AU62724/96A patent/AU697882B2/en not_active Expired
- 1996-06-06 WO PCT/US1996/010035 patent/WO1996041016A1/en not_active Ceased
- 1996-06-07 US US08/660,402 patent/US5834193A/en not_active Expired - Lifetime
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2007
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| WO1996041016A1 (en) | 1996-12-19 |
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| JP4294092B2 (ja) | 2009-07-08 |
| EP0774014A1 (en) | 1997-05-21 |
| AU697882B2 (en) | 1998-10-22 |
| MX9700950A (es) | 1998-01-31 |
| US5834193A (en) | 1998-11-10 |
| CA2196898A1 (en) | 1996-12-19 |
| JP2008119005A (ja) | 2008-05-29 |
| JPH10507085A (ja) | 1998-07-14 |
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