CA2201963A1 - Cationic oligonucleotides, and related methods of synthesis and use - Google Patents
Cationic oligonucleotides, and related methods of synthesis and useInfo
- Publication number
- CA2201963A1 CA2201963A1 CA002201963A CA2201963A CA2201963A1 CA 2201963 A1 CA2201963 A1 CA 2201963A1 CA 002201963 A CA002201963 A CA 002201963A CA 2201963 A CA2201963 A CA 2201963A CA 2201963 A1 CA2201963 A1 CA 2201963A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- oligonucleotide
- alkyl
- cationic
- alkylene
- 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.)
- Abandoned
Links
- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 142
- 125000002091 cationic group Chemical group 0.000 title claims abstract description 115
- 238000000034 method Methods 0.000 title claims abstract description 31
- 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 description 49
- 230000015572 biosynthetic process Effects 0.000 title description 23
- 238000003786 synthesis reaction Methods 0.000 title description 10
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 34
- 125000004437 phosphorous atom Chemical group 0.000 claims abstract description 26
- 125000000129 anionic group Chemical group 0.000 claims abstract description 25
- 238000007899 nucleic acid hybridization Methods 0.000 claims abstract description 16
- 238000003556 assay Methods 0.000 claims abstract description 15
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 46
- 229910052717 sulfur Inorganic materials 0.000 claims description 45
- 229910052760 oxygen Inorganic materials 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 29
- 150000007523 nucleic acids Chemical class 0.000 claims description 23
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 22
- 125000004450 alkenylene group Chemical group 0.000 claims description 22
- 125000004419 alkynylene group Chemical group 0.000 claims description 22
- 102000039446 nucleic acids Human genes 0.000 claims description 22
- 108020004707 nucleic acids Proteins 0.000 claims description 22
- 239000000523 sample Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000003729 nucleotide group Chemical group 0.000 claims description 11
- 150000008300 phosphoramidites Chemical class 0.000 claims description 11
- 229910052711 selenium Inorganic materials 0.000 claims description 10
- 238000010898 silica gel chromatography Methods 0.000 claims description 9
- 108020005187 Oligonucleotide Probes Proteins 0.000 claims description 6
- 239000002751 oligonucleotide probe Substances 0.000 claims description 6
- 239000012491 analyte Substances 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 230000000692 anti-sense effect Effects 0.000 abstract description 12
- 150000001875 compounds Chemical class 0.000 abstract description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 107
- 239000011780 sodium chloride Substances 0.000 description 53
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
- 150000003839 salts Chemical class 0.000 description 25
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- -1 phosphotriesters Chemical class 0.000 description 19
- 230000007704 transition Effects 0.000 description 18
- 108020004414 DNA Proteins 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000009396 hybridization Methods 0.000 description 15
- 239000000539 dimer Substances 0.000 description 14
- 238000004809 thin layer chromatography Methods 0.000 description 14
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 13
- 150000004713 phosphodiesters Chemical class 0.000 description 13
- 108091034057 RNA (poly(A)) Proteins 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 229940104230 thymidine Drugs 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 125000002947 alkylene group Chemical group 0.000 description 8
- 238000010494 dissociation reaction Methods 0.000 description 8
- 230000005593 dissociations Effects 0.000 description 8
- 239000002777 nucleoside Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000011574 phosphorus Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- SXUXMRMBWZCMEN-ZOQUXTDFSA-N 2'-O-methyluridine Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-ZOQUXTDFSA-N 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000004007 reversed phase HPLC Methods 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
- 108091093037 Peptide nucleic acid Proteins 0.000 description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000001142 circular dichroism spectrum Methods 0.000 description 5
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- 108091033319 polynucleotide Proteins 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 101710163270 Nuclease Proteins 0.000 description 4
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- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
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- SXUXMRMBWZCMEN-UHFFFAOYSA-N 2'-O-methyl uridine Natural products COC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 SXUXMRMBWZCMEN-UHFFFAOYSA-N 0.000 description 3
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- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical class NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
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- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
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- 230000001590 oxidative effect Effects 0.000 description 1
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- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
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- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 description 1
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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
-
- 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
-
- 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
- C12Q1/6813—Hybridisation assays
- C12Q1/6839—Triple helix formation or other higher order conformations in hybridisation assays
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US190195P | 1995-08-04 | 1995-08-04 | |
| US08/693,831 | 1996-07-31 | ||
| US08/693,831 US6017700A (en) | 1995-08-04 | 1996-07-31 | Cationic oligonucleotides, and related methods of synthesis and use |
| US60/001,901 | 1996-07-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2201963A1 true CA2201963A1 (en) | 1997-02-20 |
Family
ID=26669648
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002201963A Abandoned CA2201963A1 (en) | 1995-08-04 | 1996-08-01 | Cationic oligonucleotides, and related methods of synthesis and use |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6017700A (enExample) |
| EP (1) | EP0785942A1 (enExample) |
| JP (2) | JPH10509740A (enExample) |
| AU (1) | AU702309B2 (enExample) |
| CA (1) | CA2201963A1 (enExample) |
| WO (1) | WO1997006183A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU3090102A (en) * | 2000-12-14 | 2002-06-24 | Gen Probe Inc | Method and kit for enhancing the association rates of polynucleotides |
| CA2494571C (en) * | 2003-12-02 | 2010-02-09 | F.Hoffmann-La Roche Ag | Oligonucleotides containing molecular rods |
| WO2008008476A2 (en) * | 2006-07-12 | 2008-01-17 | The Regents Of The University Of California | Transducible delivery of nucleic acids by reversible phosphotriester charge neutralization protecting groups |
| RU2015151857A (ru) | 2008-12-02 | 2019-01-15 | Уэйв Лайф Сайенсес Джапан, Инк. | Способ синтеза модифицированных по атому фосфора нуклеиновых кислот |
| MX342945B (es) | 2009-07-06 | 2016-10-18 | Ontorii Inc * | Profármacos de ácido nucleico novedosos y métodos de uso de los mismos. |
| US10428019B2 (en) | 2010-09-24 | 2019-10-01 | Wave Life Sciences Ltd. | Chiral auxiliaries |
| EP3348564A1 (en) * | 2011-05-10 | 2018-07-18 | Bonac Corporation | Process for preparing phosphate compound bearing isotope |
| EP3248982A1 (en) | 2011-07-19 | 2017-11-29 | Wave Life Sciences Ltd. | Thiosulfonate reagents for the synthesis of functionalized nucleic acids |
| CA2879023C (en) | 2012-07-13 | 2017-03-28 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| CA2879066C (en) | 2012-07-13 | 2019-08-13 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
| CN104661664B (zh) | 2012-07-13 | 2020-07-03 | 波涛生命科学有限公司 | 手性控制 |
| CA2880869A1 (en) | 2012-08-20 | 2014-02-27 | The Regents Of The University Of California | Polynucleotides having bioreversible groups |
| KR102285326B1 (ko) | 2013-06-28 | 2021-08-04 | 에트리스 게엠베하 | Rna를 세포에 도입하기 위한 조성물 |
| US9410172B2 (en) | 2013-09-16 | 2016-08-09 | General Electric Company | Isothermal amplification using oligocation-conjugated primer sequences |
| US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| US10322173B2 (en) | 2014-01-15 | 2019-06-18 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| MX2016009290A (es) | 2014-01-16 | 2017-02-28 | Wave Life Sciences Ltd | Diseño quiral. |
| US20170056526A1 (en) | 2014-02-26 | 2017-03-02 | Ethris Gmbh | Compositions for gastrointestinal administration of rna |
| EP3034539A1 (en) | 2014-12-19 | 2016-06-22 | Ethris GmbH | Compositions for introducing nucleic acid into cells |
| KR20190058477A (ko) | 2016-08-17 | 2019-05-29 | 솔스티스 바이올로직스, 리미티드 | 폴리뉴클레오티드 구축물 |
| AU2018252193B2 (en) | 2017-04-14 | 2024-12-12 | Tallac Therapeutics, Inc. | Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use |
| WO2019006455A1 (en) | 2017-06-30 | 2019-01-03 | Solstice Biologics, Ltd. | AUXILIARIES OF CHIRAL PHOSPHORAMIDITIS AND METHODS OF USE THEREOF |
| BR112020021037A2 (pt) | 2018-04-25 | 2021-01-19 | Ethris Gmbh | Composição, composição sólida, processo para a preparação de uma composição, método para preservar uma formulação de nano ou micropartícula de um agente terapeuticamente ativo, uso de um composto selecionado de alcanos c3-c5 substituídos com um ou dois grupos hidróxi, e, dispositivo |
| EP4297722A1 (en) | 2021-02-26 | 2024-01-03 | Ethris GmbH | Formulations for aerosol formation and aerosols for the delivery of nucleic acid |
| JPWO2022230990A1 (enExample) * | 2021-04-28 | 2022-11-03 | ||
| JP2025529925A (ja) | 2022-08-26 | 2025-09-09 | エスリス ゲーエムベーハー | 安定な脂質またはリピドイドナノ粒子懸濁液 |
| EP4327829A1 (en) | 2022-08-26 | 2024-02-28 | Ethris GmbH | Stabilization of lipid or lipidoid nanoparticle suspensions |
| WO2025045767A1 (en) | 2023-08-25 | 2025-03-06 | Ethris Gmbh | Stabilized lipid and lipidoid nanoparticle formulations with specific surfactant properties for enhanced pharmaceutical applications |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2586704B1 (fr) * | 1985-09-04 | 1987-12-18 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation et a un groupe chimique activable, leur synthese et leurs applications a titre de nucleases artificielles specifiques de sequences. centre national de la recherche scientifique (cnrs) |
| US4868105A (en) * | 1985-12-11 | 1989-09-19 | Chiron Corporation | Solution phase nucleic acid sandwich assay |
| DE3916871A1 (de) * | 1989-05-24 | 1990-11-29 | Boehringer Mannheim Gmbh | Modifiziertes phosphoramidit-verfahren zur herstellung von modifizierten nukleinsaeuren |
| US4958013A (en) * | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
| AU3144593A (en) * | 1991-11-25 | 1993-06-28 | Pharmagenics, Inc. | Oligonucleotides having aminohydrocarbon phosphonate moieties |
-
1996
- 1996-07-31 US US08/693,831 patent/US6017700A/en not_active Expired - Lifetime
- 1996-08-01 CA CA002201963A patent/CA2201963A1/en not_active Abandoned
- 1996-08-01 WO PCT/US1996/013056 patent/WO1997006183A1/en not_active Ceased
- 1996-08-01 AU AU68971/96A patent/AU702309B2/en not_active Ceased
- 1996-08-01 EP EP96929675A patent/EP0785942A1/en not_active Withdrawn
- 1996-08-01 JP JP9508693A patent/JPH10509740A/ja not_active Expired - Lifetime
-
2007
- 2007-08-09 JP JP2007208670A patent/JP2008013571A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO1997006183A1 (en) | 1997-02-20 |
| US6017700A (en) | 2000-01-25 |
| JPH10509740A (ja) | 1998-09-22 |
| AU702309B2 (en) | 1999-02-18 |
| EP0785942A1 (en) | 1997-07-30 |
| JP2008013571A (ja) | 2008-01-24 |
| AU6897196A (en) | 1997-03-05 |
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