WO1993014768A1 - Procedes et compositions supprimant l'activite biologique d'une proteine de liaison d'acide nucleique intracellulaire dans une cellule, et procedes et compositions utilises pour reguler une fonction genique - Google Patents
Procedes et compositions supprimant l'activite biologique d'une proteine de liaison d'acide nucleique intracellulaire dans une cellule, et procedes et compositions utilises pour reguler une fonction genique Download PDFInfo
- Publication number
- WO1993014768A1 WO1993014768A1 PCT/US1993/000440 US9300440W WO9314768A1 WO 1993014768 A1 WO1993014768 A1 WO 1993014768A1 US 9300440 W US9300440 W US 9300440W WO 9314768 A1 WO9314768 A1 WO 9314768A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- protein
- biological activity
- cell
- dna
- rna
- Prior art date
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 97
- 238000000034 method Methods 0.000 title claims abstract description 50
- 230000003834 intracellular effect Effects 0.000 title claims abstract description 38
- 230000004071 biological effect Effects 0.000 title claims abstract description 21
- 102000044158 nucleic acid binding protein Human genes 0.000 title claims abstract description 19
- 108700020942 nucleic acid binding protein Proteins 0.000 title claims abstract description 19
- 230000003472 neutralizing effect Effects 0.000 title claims abstract description 9
- 239000000203 mixture Substances 0.000 title claims description 20
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 49
- 108020004414 DNA Proteins 0.000 claims description 50
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 42
- 108091034117 Oligonucleotide Proteins 0.000 claims description 14
- 241001465754 Metazoa Species 0.000 claims description 12
- 102000053602 DNA Human genes 0.000 claims description 11
- 102000039446 nucleic acids Human genes 0.000 claims description 8
- 108020004707 nucleic acids Proteins 0.000 claims description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 7
- 108091023040 Transcription factor Proteins 0.000 claims description 7
- 102000040945 Transcription factor Human genes 0.000 claims description 7
- 230000004069 differentiation Effects 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 7
- 238000012545 processing Methods 0.000 claims description 7
- 101710135898 Myc proto-oncogene protein Proteins 0.000 claims description 6
- 102100038895 Myc proto-oncogene protein Human genes 0.000 claims description 6
- 101710150448 Transcriptional regulator Myc Proteins 0.000 claims description 5
- 230000033228 biological regulation Effects 0.000 claims description 5
- 108010087776 Proto-Oncogene Proteins c-myb Proteins 0.000 claims description 3
- 102000009096 Proto-Oncogene Proteins c-myb Human genes 0.000 claims description 3
- 108020004682 Single-Stranded DNA Proteins 0.000 claims description 3
- 230000003054 hormonal effect Effects 0.000 claims description 3
- 101100174184 Serratia marcescens fosA gene Proteins 0.000 claims description 2
- 241000700605 Viruses Species 0.000 claims description 2
- 101150078861 fos gene Proteins 0.000 claims description 2
- 230000012010 growth Effects 0.000 claims description 2
- 230000036737 immune function Effects 0.000 claims description 2
- 239000002773 nucleotide Substances 0.000 claims description 2
- 125000003729 nucleotide group Chemical group 0.000 claims description 2
- 230000027455 binding Effects 0.000 abstract description 8
- 210000004027 cell Anatomy 0.000 description 50
- 235000018102 proteins Nutrition 0.000 description 31
- 238000013518 transcription Methods 0.000 description 14
- 230000035897 transcription Effects 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 11
- 241000196324 Embryophyta Species 0.000 description 9
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000000692 anti-sense effect Effects 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 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 description 6
- 230000004568 DNA-binding Effects 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 4
- 241000206602 Eukaryota Species 0.000 description 4
- 101100444898 Mus musculus Egr1 gene Proteins 0.000 description 4
- 102000052575 Proto-Oncogene Human genes 0.000 description 4
- 108700020978 Proto-Oncogene Proteins 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 108020005544 Antisense RNA Proteins 0.000 description 3
- 108090000994 Catalytic RNA Proteins 0.000 description 3
- 102000053642 Catalytic RNA Human genes 0.000 description 3
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108700005087 Homeobox Genes Proteins 0.000 description 3
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 102000009572 RNA Polymerase II Human genes 0.000 description 3
- 108010009460 RNA Polymerase II Proteins 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003184 complementary RNA Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 108091092562 ribozyme Proteins 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 2
- 101710149951 Protein Tat Proteins 0.000 description 2
- 102000009092 Proto-Oncogene Proteins c-myc Human genes 0.000 description 2
- 108010087705 Proto-Oncogene Proteins c-myc Proteins 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 101150036080 at gene Proteins 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 102000034356 gene-regulatory proteins Human genes 0.000 description 2
- 108091006104 gene-regulatory proteins Proteins 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- 241000269350 Anura Species 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 102000009331 Homeodomain Proteins Human genes 0.000 description 1
- 108010048671 Homeodomain Proteins Proteins 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 102000006290 Transcription Factor TFIID Human genes 0.000 description 1
- 108010083268 Transcription Factor TFIID Proteins 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 101710185494 Zinc finger protein Proteins 0.000 description 1
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 1
- 108091007916 Zinc finger transcription factors Proteins 0.000 description 1
- 102000038627 Zinc finger transcription factors Human genes 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000004102 animal cell Anatomy 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
- 230000001363 autoimmune Effects 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000001726 chromosome structure Anatomy 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000010039 intracellular degradation Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000001167 myeloblast Anatomy 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
- C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
-
- 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
- C12N2310/13—Decoys
-
- 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
- C12N2310/321—2'-O-R Modification
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16311—Human Immunodeficiency Virus, HIV concerning HIV regulatory proteins
- C12N2740/16322—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Definitions
- RNA transcripts in the cell nucleus are also important in eukaryotic gene control.
- chromosomal segments are amplified or rearranged so as to effect gene expression.
- Intracellular immunization the genetic alteration of cells that is mediated by gene transfer and leads to the inhibition of viral replication has been termed "intracellular immunization" .
- Intracellular immunization is perceived as being achievable by stable introduction of DNA into cells whose continuous expression results in the inhibition of an essential viral gene.
- antisense RNA see eintraub et al. Trends Genet. (1985) 2:22-25; Green et al, Annu. Rev. Bioche . (1986), .55:569-597; van der Krol et al. Bio. Technigues (1988), 6 .
- DNA-binding proteins exhibit a limited number of structural designs.
- Three general structural designs have been found in DNA-binding proteins: the helix-turn-helix, the zinc-finger, and the amphipathic helix motifs.
- Helix-turn-helix proteins possess a remarkably conserved region encoding about 60 amino acids, called the homeobox, which is conserved well enough to be easily recognized in genes from frogs to mammals. These homeobox proteins are believed to contact specific DNA sequences.
- Zinc-finger proteins and amphipathic helical proteins, including leucine-zipper and helix-loop-helix proteins are also known to be regulatory proteins.
- compositions of the present invention have broad applications for both unicellular and multicellular organisms, including, in particular, therapeutic potential for the latter.
- the present invention can be applied to yeast and bacterial systems as well as to either plants or animals.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Procédé de suppression de l'activité biologique d'une protéine de liaison d'acide nucléique intracellulaire dans une cellule, et qui consiste à exposer cette protéine à une concentration intracellulaire d'un ADN ou d'un ARN simple-brin (sb), ou d'un ADN ou d'un ARN double-brin (db) présentant un motif de reconnaissance par rapport à la protéine, lequel est suffisant pour effectuer la liaison de la protéine à l'ADN (sb), l'ARN (sb), ADN (db) ou l'ARN (db), ce qui permet de bloquer l'activité de la protéine intracellulaire.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US82607092A | 1992-01-27 | 1992-01-27 | |
US826,070 | 1992-01-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1993014768A1 true WO1993014768A1 (fr) | 1993-08-05 |
Family
ID=25245620
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1993/000440 WO1993014768A1 (fr) | 1992-01-27 | 1993-01-27 | Procedes et compositions supprimant l'activite biologique d'une proteine de liaison d'acide nucleique intracellulaire dans une cellule, et procedes et compositions utilises pour reguler une fonction genique |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU3584993A (fr) |
WO (1) | WO1993014768A1 (fr) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0733370A1 (fr) * | 1993-10-29 | 1996-09-25 | Shunichi Shiozawa | Inhibiteur antagoniste de la croissance des cellules mesenchymateuses |
EP0732929A1 (fr) * | 1993-10-29 | 1996-09-25 | Victor J. Dzau | Utilisation therapeutique de leurres d'elements cis in vivo |
EP0776335A1 (fr) * | 1994-08-18 | 1997-06-04 | Ariad Gene Therapeutics, Inc. | Elimination modulable d'expression genique, de fonction de produit genique, et de cellules hotes obtenues par genie genetique |
EP0805160A1 (fr) * | 1996-05-01 | 1997-11-05 | FUJIREBIO Inc. | Polypeptide lié à l'aide nucléique, procédé de préparation d'un polypeptide lié à l'acide nucléique et immunoessai utilisant le polypeptide |
US5859226A (en) * | 1993-07-29 | 1999-01-12 | Regents Of The University Of California, The | Polynucleotide decoys that inhibit MHC-II expression and uses thereof |
WO2002018607A2 (fr) * | 2000-08-30 | 2002-03-07 | North Carolina State University | Plantes transgeniques contenant des leurres moleculaires qui modifient la teneur en proteines |
US6410721B1 (en) | 1993-07-29 | 2002-06-25 | The Regents Of The University Of California | Polynucleotide decoys that inhibit MHC-II expression and uses thereof |
US7045363B2 (en) * | 1996-05-01 | 2006-05-16 | Fujirebio Inc. | Nucleic acid-bound polypeptide method of producing nucleic acid-bound polypeptide and immunoassay using the polypeptide |
US7189570B2 (en) | 2000-11-07 | 2007-03-13 | North Carolina State University | Putrescine-n-methyltransferase promoter |
US7304220B2 (en) | 1997-06-12 | 2007-12-04 | North Carolina State University | Regulation of quinolate phosphoribosyl transferase expression |
US7615538B2 (en) | 1993-10-29 | 2009-11-10 | Shunichi Shiozawa | Method for therapy of rheumatoid arthritis |
-
1993
- 1993-01-27 WO PCT/US1993/000440 patent/WO1993014768A1/fr active Application Filing
- 1993-01-27 AU AU35849/93A patent/AU3584993A/en not_active Abandoned
Non-Patent Citations (4)
Title |
---|
JOURNAL OF IMMUNOLOGY, Volume 140, No. 7, issued 01 April 1988, A. HAREL-BELLAN et al., "Specific Inhibition of C-Myc Protein Biosynthesis Using an Antisense Synthetic Deoxy-Oligonucleotide in Human T Lymphocytes", pages 2431-2435. * |
PROCEEDINGS NATIONAL ACADEMY OF SCIENCES, Volume 83, issued July 1986, J.T. HOLT et al., "Inducible Production of C-Fos Antisense RNA Inhibits 3T3 Cell Proliferation", pages 4794-4798. * |
PROCEEDINGS NATIONAL ACADEMY OF SCIENCES, Volume 86, issued May 1989, G. ANFOSSI et al., "An Oligomer Complementary to C-Myb-Encoded mRNA Inhibits Proliferation of Human Myeloid Leukemia Cell Lines", pages 3379-3383. * |
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, Volume 88, issued May 1991, L. HAN et al., "Inhibition of Moloney Murine Leukemia Virus-Induced Leukemia in Transgenic Mice Expressing Antisense RNA Complementary to the Retroviral Packaging Sequences", pages 4313-4317. * |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5859226A (en) * | 1993-07-29 | 1999-01-12 | Regents Of The University Of California, The | Polynucleotide decoys that inhibit MHC-II expression and uses thereof |
US6410721B1 (en) | 1993-07-29 | 2002-06-25 | The Regents Of The University Of California | Polynucleotide decoys that inhibit MHC-II expression and uses thereof |
EP1350514A2 (fr) * | 1993-10-29 | 2003-10-08 | The Brigham And Women's Hospital, Inc. | Utilisation thérapeutique de leurres d'élements cis in vivo |
EP0732929A1 (fr) * | 1993-10-29 | 1996-09-25 | Victor J. Dzau | Utilisation therapeutique de leurres d'elements cis in vivo |
EP1340505A3 (fr) * | 1993-10-29 | 2004-07-14 | The Brigham And Women's Hospital, Inc. | Utilisation thérapeutique de leurres d'éléments-cis in vivo |
US6821956B2 (en) | 1993-10-29 | 2004-11-23 | The Brigham And Women's Hospital, Inc. | Therapeutic use of cis-element decoys in vivo |
EP0733370A4 (fr) * | 1993-10-29 | 1999-12-29 | Shunichi Shiozawa | Inhibiteur antagoniste de la croissance des cellules mesenchymateuses |
EP0732929A4 (fr) * | 1993-10-29 | 2001-11-14 | Victor J Dzau | Utilisation therapeutique de leurres d'elements cis in vivo |
US7615538B2 (en) | 1993-10-29 | 2009-11-10 | Shunichi Shiozawa | Method for therapy of rheumatoid arthritis |
EP1350514A3 (fr) * | 1993-10-29 | 2004-07-07 | The Brigham And Women's Hospital, Inc. | Utilisation thérapeutique de leurres d'élements cis in vivo |
US6774118B1 (en) | 1993-10-29 | 2004-08-10 | The Brigham And Women's Hospital, Inc. | Therapeutic use of CIS-element decoys in vivo |
EP1340505A2 (fr) * | 1993-10-29 | 2003-09-03 | The Brigham And Women's Hospital, Inc. | Utilisation thérapeutique de leurres d'éléments-cis in vivo |
EP0733370A1 (fr) * | 1993-10-29 | 1996-09-25 | Shunichi Shiozawa | Inhibiteur antagoniste de la croissance des cellules mesenchymateuses |
EP0776335A4 (fr) * | 1994-08-18 | 1999-09-15 | Ariad Gene Therapeutics Inc | Elimination modulable d'expression genique, de fonction de produit genique, et de cellules hotes obtenues par genie genetique |
EP0776335A1 (fr) * | 1994-08-18 | 1997-06-04 | Ariad Gene Therapeutics, Inc. | Elimination modulable d'expression genique, de fonction de produit genique, et de cellules hotes obtenues par genie genetique |
US7045363B2 (en) * | 1996-05-01 | 2006-05-16 | Fujirebio Inc. | Nucleic acid-bound polypeptide method of producing nucleic acid-bound polypeptide and immunoassay using the polypeptide |
EP0805160A1 (fr) * | 1996-05-01 | 1997-11-05 | FUJIREBIO Inc. | Polypeptide lié à l'aide nucléique, procédé de préparation d'un polypeptide lié à l'acide nucléique et immunoessai utilisant le polypeptide |
US7408098B2 (en) | 1997-06-12 | 2008-08-05 | North Carolina State University | Regulation of quinolate phosphoribosyl transferase expression |
US7304220B2 (en) | 1997-06-12 | 2007-12-04 | North Carolina State University | Regulation of quinolate phosphoribosyl transferase expression |
US7425670B2 (en) | 1997-06-12 | 2008-09-16 | North Carolina State University | Methods and compositions for protein production in tobacco plants with reduced nicotine |
US7605308B2 (en) | 1997-06-12 | 2009-10-20 | North Carolina State University | Regulation of quinolate phosphoribosyl transferase expression |
US6911541B2 (en) | 2000-08-30 | 2005-06-28 | North Carolina State University | Promoter fragment that is recognized by the product of the tobacco Nic gene |
US7192771B2 (en) | 2000-08-30 | 2007-03-20 | North Carolina State University | Plant promoter sequence |
CN1330753C (zh) * | 2000-08-30 | 2007-08-08 | 北卡罗莱纳州立大学 | 含有可改变蛋白含量的分子诱导物的转基因植物 |
WO2002018607A3 (fr) * | 2000-08-30 | 2003-02-27 | Univ North Carolina State | Plantes transgeniques contenant des leurres moleculaires qui modifient la teneur en proteines |
WO2002018607A2 (fr) * | 2000-08-30 | 2002-03-07 | North Carolina State University | Plantes transgeniques contenant des leurres moleculaires qui modifient la teneur en proteines |
US7189570B2 (en) | 2000-11-07 | 2007-03-13 | North Carolina State University | Putrescine-n-methyltransferase promoter |
Also Published As
Publication number | Publication date |
---|---|
AU3584993A (en) | 1993-09-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Nuell et al. | Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and HeLa cells | |
DE69933653T2 (de) | Zur Hemmung der Expression des CCR5-Rezeptors befähigte Ribozyme | |
Lyngstadaas et al. | A synthetic, chemically modified ribozyme eliminates amelogenin, the major translation product in developing mouse enamel in vivo. | |
Ou et al. | Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs | |
Reines et al. | The RNA polymerase II general elongation factors | |
Dairaghi et al. | Addition of a 29 residue carboxyl-terminal tail converts a simple HMG box-containing protein into a transcriptional activator | |
US5596079A (en) | Mimetics of senescent cell derived inhibitors of DNA synthesis | |
Dolecki et al. | Stage‐specific expression of a homeo box‐containing gene in the non‐segmented sea urchin embryo. | |
JP3865766B2 (ja) | 老化細胞由来dna合成阻害因子 | |
McGarvey et al. | PTCH gene mutations in invasive transitional cell carcinoma of the bladder | |
AU746791B2 (en) | Transcription factor decoy and tumor growth inhibitor | |
Yoshizumi et al. | The ATF site mediates downregulation of the cyclin A gene during contact inhibition in vascular endothelial cells | |
CA2420656A1 (fr) | Oligonucleotides antisens contre vr1 | |
Bingle et al. | Cytokine-Mediated Induction of the Human Elafin Gene in Pulmonary Epithelial Cells Is Regulated by Nuclear Factor-κ B | |
US20090197336A1 (en) | Suppression of polymorphic alleles | |
WO1993014768A1 (fr) | Procedes et compositions supprimant l'activite biologique d'une proteine de liaison d'acide nucleique intracellulaire dans une cellule, et procedes et compositions utilises pour reguler une fonction genique | |
HUP0103465A2 (hu) | A VEGF expressziójának gátlására szolgáló rövid oligonukleotidok | |
WO2003042385A2 (fr) | Extinction genique au moyen de constructions hybrides d'adn sens et d'arn antisens | |
Bailly et al. | The influence of the 2‐amino group of guanine on DNA conformation. Uranyl and DNase I probing of inosine/diaminopurine substituted DNA. | |
JPH05507203A (ja) | 真核性発現ベクター系 | |
KR19990063284A (ko) | 사이클린-의존성 키나제의 억제인자에 대한 결합 파트너 및억제인자 검출 및 질병의 진단 또는 치료를 위한 이의 용도 | |
J. Tymms et al. | Regulation of gene expression by transcription factors Ets‐1 and Ets‐2 | |
Soeda et al. | Sequences from the genome of a non-transforming mutant of polyoma virus | |
Zhu et al. | Drosophila SAP18, a member of the Sin3/Rpd3 histone deacetylase complex, interacts with Bicoid and inhibits its activity. | |
Huang et al. | Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU BB BG BR CA CZ FI HU JP KP KR LK MG MN MW NO NZ PL RO RU SD SK UA US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
122 | Ep: pct application non-entry in european phase | ||
NENP | Non-entry into the national phase |
Ref country code: CA |