CA2058632A1 - Exonuclease-resistant oligonucleotides and methods for preparing the same - Google Patents
Exonuclease-resistant oligonucleotides and methods for preparing the sameInfo
- Publication number
- CA2058632A1 CA2058632A1 CA002058632A CA2058632A CA2058632A1 CA 2058632 A1 CA2058632 A1 CA 2058632A1 CA 002058632 A CA002058632 A CA 002058632A CA 2058632 A CA2058632 A CA 2058632A CA 2058632 A1 CA2058632 A1 CA 2058632A1
- Authority
- CA
- Canada
- Prior art keywords
- exonuclease
- preparing
- methods
- same
- oligonucleotide
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- 108091034117 Oligonucleotide Proteins 0.000 title abstract 6
- 108060002716 Exonuclease Proteins 0.000 title abstract 3
- 102000013165 exonuclease Human genes 0.000 title abstract 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 title abstract 2
- 238000000034 method Methods 0.000 title abstract 2
- 230000015556 catabolic process Effects 0.000 abstract 2
- 238000006731 degradation reaction Methods 0.000 abstract 2
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 abstract 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical compound OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 abstract 1
- 230000000295 complement effect Effects 0.000 abstract 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 238000009396 hybridization Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
A method is provided for making 3' and/or 5' end-capped oligonucleotides so as to render the oligonucleotide resistant to degradation by exonucleases. The exonuclease degradation resistance is provided by incorporating two or more phosphoramidate and phosphoromonothioate and/or phosphorodithioate linkages at the 5' and/or 3' ends of the oligonucleotide, wherein the number of phosphoramidate linkages is less than a number which would interfere with hybridization to a complementary oligon-ucleotide strand and/or which would interfere with RNAseH activity when the oligonucleotide is hybridized to RNA.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36104589A | 1989-06-05 | 1989-06-05 | |
| US361,045 | 1989-06-05 | ||
| PCT/US1990/003138 WO1990015065A1 (en) | 1989-06-05 | 1990-06-05 | Exonuclease-resistant oligonucleotides and methods for preparing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2058632A1 true CA2058632A1 (en) | 1990-12-06 |
| CA2058632C CA2058632C (en) | 2004-08-24 |
Family
ID=23420432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002058632A Expired - Lifetime CA2058632C (en) | 1989-06-05 | 1990-06-05 | Exonuclease-resistant oligonucleotides and methods for preparing the same |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0476071A4 (en) |
| JP (1) | JPH05500799A (en) |
| KR (1) | KR920701230A (en) |
| CA (1) | CA2058632C (en) |
| WO (1) | WO1990015065A1 (en) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5220007A (en) * | 1990-02-15 | 1993-06-15 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of RNA and production of encoded polypeptides |
| US5149797A (en) * | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
| US5965722A (en) * | 1991-05-21 | 1999-10-12 | Isis Pharmaceuticals, Inc. | Antisense inhibition of ras gene with chimeric and alternating oligonucleotides |
| WO1994008003A1 (en) * | 1991-06-14 | 1994-04-14 | Isis Pharmaceuticals, Inc. | ANTISENSE OLIGONUCLEOTIDE INHIBITION OF THE ras GENE |
| US5792608A (en) * | 1991-12-12 | 1998-08-11 | Gilead Sciences, Inc. | Nuclease stable and binding competent oligomers and methods for their use |
| AU3250093A (en) | 1991-12-12 | 1993-07-19 | Gilead Sciences, Inc. | Nuclease stable and binding competent oligomers and methods for their use |
| US5434257A (en) * | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
| JPH08502723A (en) * | 1992-07-27 | 1996-03-26 | ハイブライドン インコーポレイテッド | Oligonucleotide alkylphosphonothioate |
| US5719273A (en) * | 1993-06-14 | 1998-02-17 | Nexstar Pharmaceuticals, Inc. | Palladium catalyzed nucleoside modifications methods using nucleophiles and carbon monoxide |
| US5580972A (en) * | 1993-06-14 | 1996-12-03 | Nexstar Pharmaceuticals, Inc. | Purine nucleoside modifications by palladium catalyzed methods |
| WO1995025180A1 (en) * | 1994-03-16 | 1995-09-21 | Gen-Probe Incorporated | Isothermal strand displacement nucleic acid amplification |
| US6111095A (en) | 1995-06-07 | 2000-08-29 | Merck & Co., Inc. | Capped synthetic RNA, analogs, and aptamers |
| WO1996040726A1 (en) | 1995-06-07 | 1996-12-19 | Genta Incorporated | Novel carbamate-based cationic lipids |
| CA2250923A1 (en) * | 1996-03-26 | 1997-10-02 | Gabriella Zupi | Oligonucleotide treatments and compositions for human melanoma |
| US5959100A (en) | 1996-03-27 | 1999-09-28 | Nexstar Pharmaceuticals, Inc. | Pyrimidine nucleosides as therapeutic and diagnostic agents |
| US5945527A (en) * | 1996-05-30 | 1999-08-31 | Nexstar Pharmaceuticals, Inc. | Palladium catalyzed nucleoside modification methods using nucleophiles and carbon monoxide |
| US6576752B1 (en) | 1997-02-14 | 2003-06-10 | Isis Pharmaceuticals, Inc. | Aminooxy functionalized oligomers |
| US6127533A (en) * | 1997-02-14 | 2000-10-03 | Isis Pharmaceuticals, Inc. | 2'-O-aminooxy-modified oligonucleotides |
| US6172209B1 (en) | 1997-02-14 | 2001-01-09 | Isis Pharmaceuticals Inc. | Aminooxy-modified oligonucleotides and methods for making same |
| US6007992A (en) * | 1997-11-10 | 1999-12-28 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
| US6028183A (en) | 1997-11-07 | 2000-02-22 | Gilead Sciences, Inc. | Pyrimidine derivatives and oligonucleotides containing same |
| US6867294B1 (en) | 1998-07-14 | 2005-03-15 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
| US6043352A (en) | 1998-08-07 | 2000-03-28 | Isis Pharmaceuticals, Inc. | 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides |
| US6673912B1 (en) | 1998-08-07 | 2004-01-06 | Isis Pharmaceuticals, Inc. | 2′-O-aminoethyloxyethyl-modified oligonucleotides |
| US6020483A (en) | 1998-09-25 | 2000-02-01 | Nexstar Pharmaceuticals, Inc. | Nucleoside modifications by palladium catalyzed methods |
| US6207819B1 (en) * | 1999-02-12 | 2001-03-27 | Isis Pharmaceuticals, Inc. | Compounds, processes and intermediates for synthesis of mixed backbone oligomeric compounds |
| WO2001068048A2 (en) * | 2000-03-17 | 2001-09-20 | Unilever Plc | Non-physiologic dna fragments for tanning skin |
| KR100894767B1 (en) * | 2000-09-26 | 2009-04-24 | 이데라 파마슈티칼즈, 인코포레이티드 | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
| CN101671335A (en) | 2001-05-31 | 2010-03-17 | 梅达莱克斯公司 | Cytotoxins, prodrugs, linkers and stabilizers useful therefor |
| US7255874B1 (en) | 2001-12-21 | 2007-08-14 | Closure Medical Corporation | Biocompatible polymers and adhesives: compositions, methods of making and uses related thereto |
| US7002006B2 (en) | 2003-02-12 | 2006-02-21 | Isis Pharmaceuticals, Inc. | Protection of nucleosides |
| CA2540692C (en) | 2003-06-02 | 2013-05-28 | Isis Pharmaceuticals, Inc. | Oligonucleotide synthesis with alternative solvents |
| US7125945B2 (en) | 2003-09-19 | 2006-10-24 | Varian, Inc. | Functionalized polymer for oligonucleotide purification |
| BRPI0510909A2 (en) | 2004-05-19 | 2008-12-16 | Medarex Inc | cytotoxic drug-binder binding compound, pharmaceutical formulation, method for killing a cell and method for retarding or stopping tumor growth |
| US7427675B2 (en) | 2004-08-23 | 2008-09-23 | Isis Pharmaceuticals, Inc. | Compounds and methods for the characterization of oligonucleotides |
| EP1940470B1 (en) | 2005-09-26 | 2013-04-17 | Medarex, Inc. | Antibody-drug conjugates and their use |
| US7947447B2 (en) | 2007-01-16 | 2011-05-24 | Somalogic, Inc. | Method for generating aptamers with improved off-rates |
| GB2467691A (en) | 2008-09-05 | 2010-08-11 | Aueon Inc | Methods for stratifying and annotating cancer drug treatment options |
| KR102185779B1 (en) * | 2010-04-12 | 2020-12-03 | 소마로직, 인크. | 5-position modified pyrimidines and their use |
| US9938314B2 (en) | 2013-11-21 | 2018-04-10 | Somalogic, Inc. | Cytidine-5-carboxamide modified nucleotide compositions and methods related thereto |
| US20160017394A1 (en) * | 2014-07-15 | 2016-01-21 | Life Technologies Corporation | Compositions and methods for nucleic acid assembly |
| CA2972259A1 (en) | 2014-12-26 | 2016-06-30 | Emory University | N4-hydroxycytidine and derivatives and anti-viral uses related thereto |
| WO2019113462A1 (en) | 2017-12-07 | 2019-06-13 | Emory University | N4-hydroxycytidine and derivatives and anti-viral uses related thereto |
| WO2024114305A1 (en) * | 2022-11-29 | 2024-06-06 | Vacino Biotech Co., Ltd. | Oligonucleotide therapeutics and application thereof |
| WO2025015335A1 (en) * | 2023-07-13 | 2025-01-16 | Korro Bio, Inc. | Rna-editing oligonucleotides and uses thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4415732A (en) * | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
| US4849513A (en) * | 1983-12-20 | 1989-07-18 | California Institute Of Technology | Deoxyribonucleoside phosphoramidites in which an aliphatic amino group is attached to the sugar ring and their use for the preparation of oligonucleotides containing aliphatic amino groups |
| EP0229053A1 (en) * | 1985-06-14 | 1987-07-22 | University Patents, Inc. | Method for synthesizing deoxyoligonucleotides |
| DE3855864T2 (en) * | 1987-11-30 | 1997-09-25 | Univ Iowa Res Found | DNA MOLECULES STABILIZED BY MODIFICATIONS ON THE 3'-TERMINAL PHOSPHODIESTERBINDING, THEIR USE AS NUCLEIC ACID PROBE AND AS A THERAPEUTIC AGENT FOR INHIBITING THE EXPRESSION OF SPECIFIC TARGET GENES |
-
1990
- 1990-06-05 CA CA002058632A patent/CA2058632C/en not_active Expired - Lifetime
- 1990-06-05 JP JP2509531A patent/JPH05500799A/en active Pending
- 1990-06-05 WO PCT/US1990/003138 patent/WO1990015065A1/en not_active Application Discontinuation
- 1990-06-05 KR KR1019910701767A patent/KR920701230A/en not_active Withdrawn
- 1990-06-05 EP EP19900913804 patent/EP0476071A4/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0476071A1 (en) | 1992-03-25 |
| WO1990015065A1 (en) | 1990-12-13 |
| CA2058632C (en) | 2004-08-24 |
| EP0476071A4 (en) | 1992-11-04 |
| KR920701230A (en) | 1992-08-11 |
| JPH05500799A (en) | 1993-02-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |