CA2475447A1 - Short interfering rna molecules directed towards a tissue factor coding nucleic acid - Google Patents
Short interfering rna molecules directed towards a tissue factor coding nucleic acid Download PDFInfo
- Publication number
- CA2475447A1 CA2475447A1 CA002475447A CA2475447A CA2475447A1 CA 2475447 A1 CA2475447 A1 CA 2475447A1 CA 002475447 A CA002475447 A CA 002475447A CA 2475447 A CA2475447 A CA 2475447A CA 2475447 A1 CA2475447 A1 CA 2475447A1
- Authority
- CA
- Canada
- Prior art keywords
- sirna
- seq
- rna molecules
- pharmaceutical preparation
- rna
- 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
- 108020004459 Small interfering RNA Proteins 0.000 title claims abstract description 122
- 108010000499 Thromboplastin Proteins 0.000 title claims abstract description 81
- 102000002262 Thromboplastin Human genes 0.000 title claims abstract description 81
- 239000004055 small Interfering RNA Substances 0.000 title claims description 12
- 150000007523 nucleic acids Chemical class 0.000 title claims description 10
- 102000039446 nucleic acids Human genes 0.000 title description 3
- 108020004707 nucleic acids Proteins 0.000 title description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims abstract description 62
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 26
- 108020004999 messenger RNA Proteins 0.000 claims description 62
- 239000002773 nucleotide Substances 0.000 claims description 36
- 125000003729 nucleotide group Chemical group 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 13
- 238000003776 cleavage reaction Methods 0.000 claims description 12
- 230000007017 scission Effects 0.000 claims description 12
- 230000023555 blood coagulation Effects 0.000 claims description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 7
- 238000001802 infusion Methods 0.000 claims description 7
- 238000007918 intramuscular administration Methods 0.000 claims description 7
- 239000007927 intramuscular injection Substances 0.000 claims description 7
- 239000007928 intraperitoneal injection Substances 0.000 claims description 7
- 238000001990 intravenous administration Methods 0.000 claims description 7
- 238000007920 subcutaneous administration Methods 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 6
- 239000012634 fragment Substances 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000007921 spray Substances 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 238000010521 absorption reaction Methods 0.000 claims description 3
- 239000000443 aerosol Substances 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 238000004040 coloring Methods 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 3
- 235000003599 food sweetener Nutrition 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 238000013268 sustained release Methods 0.000 claims description 3
- 239000012730 sustained-release form Substances 0.000 claims description 3
- 239000003765 sweetening agent Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 239000003981 vehicle Substances 0.000 claims description 3
- 241000282412 Homo Species 0.000 claims description 2
- 239000003978 infusion fluid Substances 0.000 claims description 2
- 230000014509 gene expression Effects 0.000 abstract description 34
- 102000040650 (ribonucleotides)n+m Human genes 0.000 abstract description 27
- 230000000694 effects Effects 0.000 description 70
- 210000004027 cell Anatomy 0.000 description 54
- 230000009368 gene silencing by RNA Effects 0.000 description 27
- 230000035772 mutation Effects 0.000 description 27
- 101000635804 Homo sapiens Tissue factor Proteins 0.000 description 24
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 24
- 238000001890 transfection Methods 0.000 description 23
- 230000030279 gene silencing Effects 0.000 description 22
- 238000012986 modification Methods 0.000 description 15
- 238000003556 assay Methods 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 11
- 108060001084 Luciferase Proteins 0.000 description 10
- 239000005089 Luciferase Substances 0.000 description 10
- 108090000994 Catalytic RNA Proteins 0.000 description 9
- 102000053642 Catalytic RNA Human genes 0.000 description 9
- 238000006731 degradation reaction Methods 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 108091092562 ribozyme Proteins 0.000 description 9
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 8
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 108091081021 Sense strand Proteins 0.000 description 7
- 238000007385 chemical modification Methods 0.000 description 7
- 210000004962 mammalian cell Anatomy 0.000 description 7
- 230000032361 posttranscriptional gene silencing Effects 0.000 description 7
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 6
- 230000002947 procoagulating effect Effects 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 102000006382 Ribonucleases Human genes 0.000 description 5
- 108010083644 Ribonucleases Proteins 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000002688 persistence Effects 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000006807 siRNA silencing Effects 0.000 description 5
- 108091027967 Small hairpin RNA Proteins 0.000 description 4
- 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 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 230000009977 dual effect Effects 0.000 description 4
- 238000012226 gene silencing method Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 125000002652 ribonucleotide group Chemical group 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 3
- 239000012983 Dulbecco’s minimal essential medium Substances 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 3
- 108091028664 Ribonucleotide Proteins 0.000 description 3
- 241000251131 Sphyrna Species 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000007069 methylation reaction Methods 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000002336 ribonucleotide Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- 102100023804 Coagulation factor VII Human genes 0.000 description 2
- 108010023321 Factor VII Proteins 0.000 description 2
- 108090001102 Hammerhead ribozyme Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000001994 activation Methods 0.000 description 2
- 238000005937 allylation reaction Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000010841 mRNA extraction Methods 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 230000000869 mutational effect Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 108010083590 Apoproteins Proteins 0.000 description 1
- 102000006410 Apoproteins Human genes 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 230000007067 DNA methylation Effects 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 235000008694 Humulus lupulus Nutrition 0.000 description 1
- 244000025221 Humulus lupulus Species 0.000 description 1
- 206010027280 Meningococcal sepsis Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 108010052090 Renilla Luciferases Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 108091060271 Small temporal RNA Proteins 0.000 description 1
- 241001150496 Tosapusia duplex Species 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 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 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002787 antisense oligonuctleotide Substances 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 101150055766 cat gene Proteins 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 229940105772 coagulation factor vii Drugs 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000005712 elicitor Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 230000004049 epigenetic modification Effects 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000037440 gene silencing effect Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000001985 kidney epithelial cell Anatomy 0.000 description 1
- 108091023663 let-7 stem-loop Proteins 0.000 description 1
- 108091063478 let-7-1 stem-loop Proteins 0.000 description 1
- 108091049777 let-7-2 stem-loop Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 230000008742 procoagulation Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000001743 silencing effect Effects 0.000 description 1
- RGHFKWPGWBFQLN-UHFFFAOYSA-M sodium;5,5-diethylpyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].CCC1(CC)C([O-])=NC(=O)NC1=O RGHFKWPGWBFQLN-UHFFFAOYSA-M 0.000 description 1
- 210000001324 spliceosome Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO20020612 | 2002-02-07 | ||
| NO20020612A NO20020612D0 (no) | 2002-02-07 | 2002-02-07 | Posttranskripsjonell inhibering ved korte interfererende RNA |
| US35451502P | 2002-02-08 | 2002-02-08 | |
| US60/354,515 | 2002-02-08 | ||
| NO20024987 | 2002-10-16 | ||
| NO20024987A NO20024987D0 (no) | 2002-02-07 | 2002-10-16 | Posttranskripsjonell inhibering ved korte interfererende RNA'er |
| PCT/NO2003/000045 WO2003066650A2 (en) | 2002-02-07 | 2003-02-06 | Short interfering rna molecules directed towards a tissue factor coding nucleic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2475447A1 true CA2475447A1 (en) | 2003-08-14 |
Family
ID=27738950
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002475447A Abandoned CA2475447A1 (en) | 2002-02-07 | 2003-02-06 | Short interfering rna molecules directed towards a tissue factor coding nucleic acid |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1554381B1 (enExample) |
| JP (1) | JP4335012B2 (enExample) |
| AT (1) | ATE449846T1 (enExample) |
| AU (1) | AU2003206267B2 (enExample) |
| CA (1) | CA2475447A1 (enExample) |
| DE (1) | DE60330263D1 (enExample) |
| DK (1) | DK1554381T3 (enExample) |
| ES (1) | ES2336440T3 (enExample) |
| WO (1) | WO2003066650A2 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1660658A2 (en) * | 2003-08-06 | 2006-05-31 | Hans Peter B. Prydz | The use of sirna silencing in the prevention of metastasis |
| US7919583B2 (en) | 2005-08-08 | 2011-04-05 | Discovery Genomics, Inc. | Integration-site directed vector systems |
| WO2010008562A2 (en) | 2008-07-16 | 2010-01-21 | Recombinetics | Methods and materials for producing transgenic animals |
| WO2011084193A1 (en) * | 2010-01-07 | 2011-07-14 | Quark Pharmaceuticals, Inc. | Oligonucleotide compounds comprising non-nucleotide overhangs |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6387366B1 (en) * | 1998-12-31 | 2002-05-14 | Alg Company | Methods for reducing adverse side effects associated with cellular transplantation |
| EP1429650B1 (en) * | 2001-08-30 | 2009-06-24 | Mount Sinai School of Medicine of New York University | Alternatively spliced circulating tissue factor |
-
2003
- 2003-02-06 AU AU2003206267A patent/AU2003206267B2/en not_active Ceased
- 2003-02-06 EP EP03703543A patent/EP1554381B1/en not_active Expired - Lifetime
- 2003-02-06 WO PCT/NO2003/000045 patent/WO2003066650A2/en not_active Ceased
- 2003-02-06 ES ES03703543T patent/ES2336440T3/es not_active Expired - Lifetime
- 2003-02-06 CA CA002475447A patent/CA2475447A1/en not_active Abandoned
- 2003-02-06 JP JP2003566021A patent/JP4335012B2/ja not_active Expired - Fee Related
- 2003-02-06 DK DK03703543.3T patent/DK1554381T3/da active
- 2003-02-06 DE DE60330263T patent/DE60330263D1/de not_active Expired - Lifetime
- 2003-02-06 AT AT03703543T patent/ATE449846T1/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003066650A2 (en) | 2003-08-14 |
| WO2003066650A3 (en) | 2004-05-21 |
| ES2336440T3 (es) | 2010-04-13 |
| EP1554381B1 (en) | 2009-11-25 |
| JP2005532038A (ja) | 2005-10-27 |
| AU2003206267B2 (en) | 2008-10-02 |
| AU2003206267A1 (en) | 2003-09-02 |
| DE60330263D1 (de) | 2010-01-07 |
| DK1554381T3 (da) | 2010-03-29 |
| ATE449846T1 (de) | 2009-12-15 |
| EP1554381A2 (en) | 2005-07-20 |
| JP4335012B2 (ja) | 2009-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6757373B2 (ja) | キラルデザイン | |
| KR102723833B1 (ko) | 아포지단백질 C-III (APOC3)의 발현을 억제하기 위한 RNAi 작용제 및 조성물 | |
| EP2311994A1 (en) | Compositions and methods for preparing short RNA molecules and other nucleic acids | |
| US20090118206A1 (en) | Rna interference for the treatment of gain-of-function disorders | |
| JP2010525813A (ja) | 二本鎖rnaによる遺伝子発現の特異的阻害のための、方法及び組成物 | |
| CA2764456A1 (en) | Oligonucleotide duplexes comprising dna-like and rna-like nucleotides and uses thereof | |
| WO2004063375A1 (en) | OPTIMIZING siRNA BY RNAi ANTISENSE | |
| US20040224328A1 (en) | siRNA screening method | |
| US20090069263A1 (en) | 4'-thioarabinonucleotide-containing oligonucleotides, compounds and methods for their preparation and uses thereof | |
| EP1554381B1 (en) | Post transcriptional silencing of tissue factor expression by short interfering rnas | |
| US20100273998A1 (en) | Methods and compositions for modulating tissue factor | |
| WO2005040187A2 (en) | The use of sirna silencing in the prevention of metastasis | |
| US20100113558A1 (en) | Compounds and methods | |
| HK40088424A (en) | Chiral design | |
| KR20250172722A (ko) | 키랄 디자인 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |