CA2157015A1 - Co-localisation d'une molecule cible et de ses inhibiteurs - Google Patents
Co-localisation d'une molecule cible et de ses inhibiteursInfo
- Publication number
- CA2157015A1 CA2157015A1 CA002157015A CA2157015A CA2157015A1 CA 2157015 A1 CA2157015 A1 CA 2157015A1 CA 002157015 A CA002157015 A CA 002157015A CA 2157015 A CA2157015 A CA 2157015A CA 2157015 A1 CA2157015 A1 CA 2157015A1
- Authority
- CA
- Canada
- Prior art keywords
- ribozyme
- hiv
- rna
- target molecule
- molecule
- 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
- 239000003112 inhibitor Substances 0.000 title claims abstract description 25
- 230000008045 co-localization Effects 0.000 title abstract description 17
- 108090000994 Catalytic RNA Proteins 0.000 claims abstract description 109
- 102000053642 Catalytic RNA Human genes 0.000 claims abstract description 108
- 108091092562 ribozyme Proteins 0.000 claims abstract description 108
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims abstract description 61
- 230000027455 binding Effects 0.000 claims abstract description 29
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims abstract description 10
- 210000004027 cell Anatomy 0.000 claims description 36
- 238000004806 packaging method and process Methods 0.000 claims description 10
- 108091023045 Untranslated Region Proteins 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 238000006471 dimerization reaction Methods 0.000 claims description 6
- 238000011144 upstream manufacturing Methods 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 4
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- 230000003612 virological effect Effects 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 18
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- 239000003814 drug Substances 0.000 abstract description 10
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- 229940124597 therapeutic agent Drugs 0.000 abstract description 9
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- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 abstract description 5
- 231100000252 nontoxic Toxicity 0.000 abstract description 3
- 230000003000 nontoxic effect Effects 0.000 abstract description 3
- 230000002441 reversible effect Effects 0.000 abstract description 3
- 229940021747 therapeutic vaccine Drugs 0.000 abstract description 3
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- 238000001415 gene therapy Methods 0.000 description 2
- 108090001052 hairpin ribozyme Proteins 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000001524 infective effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
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- 239000001226 triphosphate Substances 0.000 description 2
- 235000011178 triphosphate Nutrition 0.000 description 2
- 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
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- 230000017613 viral reproduction Effects 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 101710205625 Capsid protein p24 Proteins 0.000 description 1
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- 108090000790 Enzymes Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241000724709 Hepatitis delta virus Species 0.000 description 1
- 102000017013 Heterogeneous Nuclear Ribonucleoprotein A1 Human genes 0.000 description 1
- 108010014594 Heterogeneous Nuclear Ribonucleoprotein A1 Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 101710177166 Phosphoprotein Proteins 0.000 description 1
- 102000014450 RNA Polymerase III Human genes 0.000 description 1
- 108010078067 RNA Polymerase III Proteins 0.000 description 1
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 1
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- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 101710149279 Small delta antigen Proteins 0.000 description 1
- 108091027544 Subgenomic mRNA Proteins 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 108091026822 U6 spliceosomal RNA Proteins 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 241000269370 Xenopus <genus> Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
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- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
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- 210000002950 fibroblast Anatomy 0.000 description 1
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- 210000005260 human cell Anatomy 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000037041 intracellular level Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 238000009828 non-uniform distribution Methods 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
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- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
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- 229960005486 vaccine Drugs 0.000 description 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
-
- 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
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases RNAses, DNAses
-
- 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
- C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
- C12Q1/701—Specific hybridization probes
- C12Q1/702—Specific hybridization probes for retroviruses
- C12Q1/703—Viruses associated with AIDS
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
- C12N2310/11—Antisense
- C12N2310/111—Antisense spanning the whole gene, or a large part of it
-
- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- AIDS & HIV (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Analytical Chemistry (AREA)
- Plant Pathology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Cette invention concerne des mécanismes permettant de co-localiser dans une cellule vivante une molécule cible et un inhibiteur de cette même molécule cible, ainsi que de nouvelles molécules de ribozyme ARNt?LYS¿ chimères qui sont en forte concurrence avec l'ARNt?LYS¿ pour les sites de liaison de la transcriptase inverse du VIH-1. Ces ribosymes d'ARNt?LYS¿ humaines chimères inhibent la tanscription inverse du VIH-1 en apportant directement à la particule du virion des inhibiteurs tels que des ribozymes de la transcriptase inverse du VIH-1 et la rendent non fonctionnelle. Les molécules chimères de cette invention servent par conséquent d'agents et de vaccins thérapeutiques non toxiques hautement spécifiques utilisables contre les infections virales, y compris lentivirales. Ces molécules chimères ont également permis de découvrir une nouvelle activité de clivage de l'ARN à spécificité de site du VIH-1.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/185,827 US5827935A (en) | 1992-05-27 | 1992-05-27 | Chimeric tRNAlys -ribozyme molecules |
US08/185,827 | 1994-01-24 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2157015A1 true CA2157015A1 (fr) | 1995-07-27 |
Family
ID=22682602
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002157015A Abandoned CA2157015A1 (fr) | 1994-01-24 | 1994-12-02 | Co-localisation d'une molecule cible et de ses inhibiteurs |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0707493A4 (fr) |
AU (1) | AU692208B2 (fr) |
CA (1) | CA2157015A1 (fr) |
WO (1) | WO1995019788A1 (fr) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7919583B2 (en) | 2005-08-08 | 2011-04-05 | Discovery Genomics, Inc. | Integration-site directed vector systems |
WO2010008562A2 (fr) | 2008-07-16 | 2010-01-21 | Recombinetics | Procédés et matériaux pour produire des animaux transgéniques |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE59010432D1 (de) * | 1989-03-16 | 1996-09-05 | Boehringer Ingelheim Int | Genetische Einheiten zur Inhibierung der Funktion von RNA |
WO1993023569A1 (fr) * | 1992-05-11 | 1993-11-25 | Ribozyme Pharmaceuticals, Inc. | Procede et reactif d'inhibition de la replication virale |
EP0596901B1 (fr) * | 1992-05-27 | 2000-08-09 | City Of Hope | MOLECULES CHIMERIQUES DE RIBOZYMES D'ARNt LYS |
-
1994
- 1994-12-02 AU AU13335/95A patent/AU692208B2/en not_active Expired
- 1994-12-02 WO PCT/US1994/013798 patent/WO1995019788A1/fr not_active Application Discontinuation
- 1994-12-02 CA CA002157015A patent/CA2157015A1/fr not_active Abandoned
- 1994-12-02 EP EP95904785A patent/EP0707493A4/fr not_active Withdrawn
Also Published As
Publication number | Publication date |
---|---|
AU692208B2 (en) | 1998-06-04 |
EP0707493A1 (fr) | 1996-04-24 |
WO1995019788A1 (fr) | 1995-07-27 |
EP0707493A4 (fr) | 1999-03-31 |
AU1333595A (en) | 1995-08-08 |
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