DE552178T1 - Abgeänderte ribozyme. - Google Patents
Abgeänderte ribozyme.Info
- Publication number
- DE552178T1 DE552178T1 DE91916858T DE91916858T DE552178T1 DE 552178 T1 DE552178 T1 DE 552178T1 DE 91916858 T DE91916858 T DE 91916858T DE 91916858 T DE91916858 T DE 91916858T DE 552178 T1 DE552178 T1 DE 552178T1
- Authority
- DE
- Germany
- Prior art keywords
- rna
- group
- modified
- nucleotide
- rna according
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 claims abstract 17
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims abstract 11
- -1 azido, amino, monosubstituted amino Chemical group 0.000 claims abstract 7
- 125000003277 amino group Chemical group 0.000 claims abstract 6
- 230000003197 catalytic effect Effects 0.000 claims abstract 5
- 239000003814 drug Substances 0.000 claims abstract 5
- 229940124597 therapeutic agent Drugs 0.000 claims abstract 5
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims abstract 3
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims abstract 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 3
- 125000003396 thiol group Chemical group [H]S* 0.000 claims abstract 3
- 102000004190 Enzymes Human genes 0.000 claims abstract 2
- 108090000790 Enzymes Proteins 0.000 claims abstract 2
- 239000011942 biocatalyst Substances 0.000 claims abstract 2
- 239000002777 nucleoside Substances 0.000 claims abstract 2
- 150000003833 nucleoside derivatives Chemical class 0.000 claims abstract 2
- 238000002360 preparation method Methods 0.000 claims abstract 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 42
- 125000003729 nucleotide group Chemical group 0.000 claims 13
- 239000002773 nucleotide Substances 0.000 claims 12
- 238000003786 synthesis reaction Methods 0.000 claims 7
- 230000015572 biosynthetic process Effects 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 150000002367 halogens Chemical class 0.000 claims 5
- 108020004707 nucleic acids Proteins 0.000 claims 4
- 102000039446 nucleic acids Human genes 0.000 claims 4
- 150000007523 nucleic acids Chemical class 0.000 claims 4
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 claims 3
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 claims 3
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 3
- 230000001419 dependent effect Effects 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 239000002243 precursor Substances 0.000 claims 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- 102100030011 Endoribonuclease Human genes 0.000 claims 2
- 108010093099 Endoribonucleases Proteins 0.000 claims 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000000969 carrier Substances 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 239000000945 filler Substances 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims 2
- 150000002500 ions Chemical class 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 1
- NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical class NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 claims 1
- RJOXFJDOUQJOMQ-UHFFFAOYSA-N 6-sulfanylidene-3,7-dihydropurin-2-one Chemical compound S=C1NC(=O)NC2=C1NC=N2 RJOXFJDOUQJOMQ-UHFFFAOYSA-N 0.000 claims 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims 1
- 102000016911 Deoxyribonucleases Human genes 0.000 claims 1
- 108010053770 Deoxyribonucleases Proteins 0.000 claims 1
- 108090001102 Hammerhead ribozyme Proteins 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims 1
- 102000003832 Nucleotidyltransferases Human genes 0.000 claims 1
- 108090000119 Nucleotidyltransferases Proteins 0.000 claims 1
- 102000006382 Ribonucleases Human genes 0.000 claims 1
- 108010083644 Ribonucleases Proteins 0.000 claims 1
- 108091027967 Small hairpin RNA Proteins 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- RTGGYPQTXNSBPD-XVFCMESISA-N [(2r,3r,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methyl dihydrogen phosphate Chemical group F[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 RTGGYPQTXNSBPD-XVFCMESISA-N 0.000 claims 1
- OWNKJJAVEHMKCW-XVFCMESISA-N [(2r,3s,4r,5r)-4-amino-5-(2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl dihydrogen phosphate Chemical compound N[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 OWNKJJAVEHMKCW-XVFCMESISA-N 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- 229940104302 cytosine Drugs 0.000 claims 1
- 238000010348 incorporation Methods 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 150000008300 phosphoramidites Chemical class 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 238000013518 transcription Methods 0.000 claims 1
- 230000035897 transcription Effects 0.000 claims 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 1
- 229940075420 xanthine Drugs 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 239000003607 modifier Substances 0.000 abstract 1
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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
- C12N15/1132—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses against retroviridae, e.g. HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/12—Type of nucleic acid catalytic nucleic acids, e.g. ribozymes
- C12N2310/121—Hammerhead
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/12—Type of nucleic acid catalytic nucleic acids, e.g. ribozymes
- C12N2310/122—Hairpin
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/322—2'-R Modification
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- AIDS & HIV (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Veterinary Medicine (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Materials Applied To Surfaces To Minimize Adherence Of Mist Or Water (AREA)
- Prostheses (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Claims (43)
1. RNA-Molekül mit katalytischer Aktivität, umfassend
mindestens ein modifiziertes Nukleosid, worin die Hydroxylgruppe an der 2'-Position des Ribosezuckers
durch eine Modifizierungsgruppe ersetzt ist, ausgewählt aus Halogen-, Sulfhydryl-, Azido-, Amino-, monosubstituierten
Amino- und disubstituierten Aminogruppen.
2. RNA nach Anspruch 1, worin die Modifzierungsgruppe
eine Halogen- oder eine Aminogruppe ist.
3. RNA nach Anspruch 1 oder 2, worin die Halogengruppe
eine Fluorgruppe ist.
4. RNA nach Anspruch 1, worin die katalytische Aktivität mindestens eine aus der Gruppe umfaßt, bestehend aus
Nukleotidyltransferase-, Dephosphorylase-, Deoxyribonuklease- und sequenzspezifischen Endoribonuklease-Aktivitäten.
5. RNA nach Anspruch 4, worin die katalytische Aktivität
eine sequenzspezifische Endoribonuklease-Aktivität umfaßt.
6. RNA nach Anspruch 5, worin sie ein Hammerkopf-Ribozym
oder eine Haarnadel-RNA ist.
7. RNA nach einem der vorhergehenden Ansprüche, worin die an den modifzierten Ribosezucker gebundene Nukleotidbase
ausgewählt ist aus der Gruppe, bestehend aus natürlich in RNA vorkommenden Basen und substituierten
Basen.
8. RNA nach Anspruch 7, worin die substituierte Nukleotidbase
ausgewählt ist aus der Gruppe, bestehend aus Xanthin, Hypoxanthin, 2,6-Diaminopurin, 2-Hydroxy-6-mercaptopurin
und Purinbasen, die an der Position 6 mit Schwefel substituiert sind, oder Pyrimidinbasen,
die an der Position 5 mit Halogen- oder C1 -C5-Alkylgruppen
substituiert sind.
9. RNA nach Anspruch 7, worin die an den modifizierten
Ribosezucker gebundene Nukleotidbase eine natürlich in RNA vorkommende Base ist.
10. RNA nach Anspruch 9, worin die an den modifizierten
Ribosezucker gebundene Nukleotidbase eine Pyrimidinbase ist.
11. RNA nach einem der vorhergehenden Ansprüche, worin alle Nukleotidbasen einer spezifischen Art an einen
modifizierten Ribosezucker gebunden sind.
12. RNA nach Anspruch 11, worin alle Uracil-Nukleotidbasen an einen modifizierten Ribosezucker gebunden sind.
13. RNA nach Anspruch 11, worin alle Cytosin-Nukleotidbasen an einen modifizierten Ribosezucker gebunden
sind.
14. RNA nach einem der Ansprüche 1 bis 10, worin alle Nukleotidbasen von zwei spezifischen Arten an einen
modifizierten Ribosezucker gebunden sind.
15. RNA nach Anspruch 14, worin alle Cytosin- und Uracil-Nukleotidbasen
an einen modifizierten Zucker gebunden sind.
16. RNA nach einem der Ansprüche 11 bis 15, worin der
modifizierte Ribosezucker eine 2'-Fluor- oder 2'-Aminogruppe umfaßt.
17. RNA, umfassend die Nukleotidseguenz E2:
5'-GGG(2'-FU)CC(2'-FU)C(2'-FU)GA(2'-FU)GAGGCCG
(2'-FU)(2'-FU)AGGCCGAAAC(2'-FU)CC-3',
worin 2'-FU 2'-Deoxy-2'-fluoruridinmonophosphat bedeutet.
18. RNA, umfassend die Nukleotidseguenz E3:
5'-GGG^'-NH2 U)CC^-NH2 U)C (2'-NH2 U)GA(^-NH2U)
GAGGCCG(2'-NH2 U)(2'-NH2 U)AGGCCGAAAC(2'-NH2 U)CC-3',
worin 2'-NH2 U 2'-Deoxy-2'-aminouridinmonophosphat
bedeutet.
19. RNA nach einem der Ansprüche 1 bis 10, umfassend ein selektives Modifikationsmuster auf Basis der strukturellen
Charakteristiken des Moleküls.
20. RNA nach Anspruch 19, worin die Nukleotide an hypersensitiven
Stellen für Ribonukleasen modifiziert sind.
21. RNA nach einem der vorhergehenden Ansprüche, weiterhin umfassend mindestens eine modifizierte internukleotidische
Phosphodiesterbindung.
22. RNA nach Anspruch 21, worin die modifizierte Phosphodiesterbindung
eine Phosphorthioatgruppe ist.
23. RNA nach Anspruch 21 oder 22, worin mindestens die 5'-terminale
Phosphodiesterbindung modifiziert ist.
24. RNA nach einem der Ansprüche 21 bis 23, worin mindestens die 3'-terminale Phosphodiesterbindung modifiziert
ist.
25. RNA nach einem der Ansprüche 21 bis 24, worin die 5'-terminale
Phosphodiesterbindung und mindestens drei
3'-terminale Phosphodiesterbindungen modifiziert
sind.
3'-terminale Phosphodiesterbindungen modifiziert
sind.
26. Verfahren zur Synthese eines RNA-Moleküls mit katalytischer
Aktivität, umfassend:
Einbauen von mindestens einem modifizierten Nukleotid
in eine RNA-Kette, worin die Hydroxylgruppe an der 2'-Position des Ribosezuckers durch eine Modifizierungsgruppe ersetzt wird, ausgewählt aus Halogen-, SuIfhydryl-,
Azido-, Amino-, monosubstituierten Amino- und
disubstituierten Aminogruppen.
disubstituierten Aminogruppen.
27. Verfahren nach Anspruch 26, worin die Modifizierungsgruppe eine Halogen- oder eine Aminogruppe ist.
28. Verfahren nach Anspruch 26 oder 27, worin die Halogengruppe eine Fluorgruppe ist.
29. Verfahren nach Anspruch 27 oder 28, worin die Synthese
der RNA-Kette durch chemische Synthese aus Nukleotidvorstufen auf einem festen Träger, Entfernen des RNA-Produkts
vom festen Träger und Reinigen des entfernten RNA-Produkts durchgeführt wird.
30. Verfahren nach Anspruch 27 oder 28, worin die Synthese der RNA-Kette durch chemische Synthese aus Nukleotidvorstufen
in Lösung und Reinigen des RNA-Produkts erfolgt.
31. Verfahren nach Anspruch 29 oder 30, worin die jeweiligen Phosphoramidite oder H-Phosphonate als Nukleotidvorstufen
verwendet werden.
32. Verfahren nach einem der Ansprüche 29 bis 31, worin die Aminomodifizierungsgruppe in eine RNA-Kette in
Form einer Trifluoracetylamidgruppe eingebaut wird und die Trifluoracetylschutzgruppe anschließend durch
Behandlung mit Ammoniak entfernt wird.
33. Verfahren nach einem der Ansprüche 26 bis 32, weiterhin umfassend:
Einbauen von mindestens einer modifizierten internukleotidischen Phosphodiesterbindung in eine RNA-Kette.
34. Verfahren nach Anspruch 33, worin die modifizierte Phosphodiesterbindung eine Phosphorthioatgruppe ist.
35. Verfahren nach einem der Ansprüche 26 bis 28, worin die Synthese der RNA-Kette durch Transkription von
einem Nukleinsäuretemplate durch eine Nukleinsäurepolymerase erfolgt.
36. Verfahren nach Anspruch 35, worin das Nukleinsäuretemplate
ein DNA-Template ist und die Nukleinsäurepolymerase eine DNA-abhängige RNA-Polymerase ist.
37. Verfahren nach Anspruch 36, worin die DNA-abhängige
RNA-Polymerase aus der Gruppe, bestehend aus T7-, T3- und SP6-Polymerase, ausgewählt wird.
38. Verfahren nach Anspruch 37, worin die DNA-abhängige RNA-Polymerase T7-Polymerase ist.
39. Verfahren nach einem der Ansprüche 35 bis 38, worin die Modifizierungsgruppe eine Halogengruppe ist und
die Synthese der RNA-Kette in Gegenwart von Mn2+-Ionen durchgeführt wird.
40. Verfahren nach einem der Ansprüche 35 bis 38, worin die Modifizierungsgruppe eine Amino-, monosubstituierte
Amino- oder disubstituierte Aminogruppe ist und die Synthese der RNA-Kette in Gegenwart von Mg2 + -Ionen
durchgeführt wird.
41. Verwendung einer RNA nach einem der Ansprüche 1 bis als therapeutisches Mittel oder Biokatalysator.
42. Therapeutisches Mittel, umfassend als Wirkstoff eine RNA nach einem der Ansprüche 1 bis 25 gegebenenfalls
zusammen mit gebräuchlichen Füllmitteln, Hilfsmitteln, Trägermitteln und Verdünnungsmitteln.
43. Verfahren zur Herstellung eines therapeutischen Mittels, worin das therapeutische Mittel als Wirkstoff
eine RNA nach einem der Ansprüche 1 bis 25, gegebenenfalls mit üblichen Füllmitteln, Hilfsmitteln, Trägermitteln
und Verdünnungsmitteln enthält.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP9001731 | 1990-10-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE552178T1 true DE552178T1 (de) | 1994-02-03 |
Family
ID=8165527
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69123979T Expired - Fee Related DE69123979T2 (de) | 1990-10-12 | 1991-09-23 | Abgeänderte ribozyme |
| DE91916858T Pending DE552178T1 (de) | 1990-10-12 | 1991-09-23 | Abgeänderte ribozyme. |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69123979T Expired - Fee Related DE69123979T2 (de) | 1990-10-12 | 1991-09-23 | Abgeänderte ribozyme |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US5672695A (de) |
| EP (1) | EP0552178B1 (de) |
| JP (2) | JP3257675B2 (de) |
| AT (1) | ATE147098T1 (de) |
| AU (1) | AU649074B2 (de) |
| CA (1) | CA2093664C (de) |
| DE (2) | DE69123979T2 (de) |
| ES (1) | ES2061416T3 (de) |
| GR (1) | GR930300130T1 (de) |
| PL (1) | PL169576B1 (de) |
| WO (1) | WO1992007065A1 (de) |
Families Citing this family (471)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4987071A (en) * | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
| AU632993B2 (en) * | 1987-12-15 | 1993-01-21 | Gene Shears Pty. Limited | Ribozymes |
| DE59010432D1 (de) * | 1989-03-16 | 1996-09-05 | Boehringer Ingelheim Int | Genetische Einheiten zur Inhibierung der Funktion von RNA |
| US5149796A (en) * | 1989-08-31 | 1992-09-22 | City Of Hope | Chimeric DNA-RNA catalytic sequences |
| CA2039718C (en) * | 1989-08-31 | 2003-02-25 | John J. Rossi | Chimeric dna-rna catalytic sequences |
| WO1991019789A1 (en) * | 1990-06-19 | 1991-12-26 | Commonwealth Scientific And Industrial Research Organisation | Endonucleases |
| JP3257675B2 (ja) * | 1990-10-12 | 2002-02-18 | マックス−プランク−ゲゼルシャフト ツール フェルデルング デル ビッセンシャフテン エー．ファウ． | 修飾リボザイム |
| DE4216134A1 (de) * | 1991-06-20 | 1992-12-24 | Europ Lab Molekularbiolog | Synthetische katalytische oligonukleotidstrukturen |
| US5817635A (en) * | 1993-08-09 | 1998-10-06 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Modified ribozymes |
-
1991
- 1991-09-23 JP JP51523691A patent/JP3257675B2/ja not_active Expired - Fee Related
- 1991-09-23 CA CA002093664A patent/CA2093664C/en not_active Expired - Fee Related
- 1991-09-23 AU AU86139/91A patent/AU649074B2/en not_active Ceased
- 1991-09-23 ES ES91916858T patent/ES2061416T3/es not_active Expired - Lifetime
- 1991-09-23 EP EP91916858A patent/EP0552178B1/de not_active Expired - Lifetime
- 1991-09-23 DE DE69123979T patent/DE69123979T2/de not_active Expired - Fee Related
- 1991-09-23 US US07/965,411 patent/US5672695A/en not_active Expired - Lifetime
- 1991-09-23 DE DE91916858T patent/DE552178T1/de active Pending
- 1991-09-23 PL PL91298867A patent/PL169576B1/pl not_active IP Right Cessation
- 1991-09-23 AT AT91916858T patent/ATE147098T1/de active
- 1991-09-23 WO PCT/EP1991/001811 patent/WO1992007065A1/en active IP Right Grant
-
1993
- 1993-12-30 GR GR930300130T patent/GR930300130T1/el unknown
-
1995
- 1995-05-04 US US08/434,501 patent/US5698687A/en not_active Expired - Lifetime
-
1997
- 1997-09-24 US US08/936,657 patent/US6890908B1/en not_active Expired - Fee Related
-
2001
- 2001-07-05 JP JP2001205286A patent/JP2002101893A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US6890908B1 (en) | 2005-05-10 |
| EP0552178A1 (de) | 1993-07-28 |
| JPH06501842A (ja) | 1994-03-03 |
| JP2002101893A (ja) | 2002-04-09 |
| WO1992007065A1 (en) | 1992-04-30 |
| DE69123979T2 (de) | 1997-04-30 |
| ES2061416T3 (es) | 1997-03-01 |
| DE69123979D1 (de) | 1997-02-13 |
| GR930300130T1 (en) | 1993-12-30 |
| US5698687A (en) | 1997-12-16 |
| CA2093664C (en) | 2003-07-29 |
| US5672695A (en) | 1997-09-30 |
| ATE147098T1 (de) | 1997-01-15 |
| ES2061416T1 (es) | 1994-12-16 |
| PL169576B1 (pl) | 1996-08-30 |
| EP0552178B1 (de) | 1997-01-02 |
| AU8613991A (en) | 1992-05-20 |
| AU649074B2 (en) | 1994-05-12 |
| JP3257675B2 (ja) | 2002-02-18 |
| CA2093664A1 (en) | 1992-04-13 |
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