NO306623B1 - Fremgangsmåte for fremstilling av DNA-molekyl inneholdende deler av et gen som transkriberes av polymerase III og en DNA-sekvens som koder for et inhiberende RNA-molekyl - Google Patents
Fremgangsmåte for fremstilling av DNA-molekyl inneholdende deler av et gen som transkriberes av polymerase III og en DNA-sekvens som koder for et inhiberende RNA-molekyl Download PDFInfo
- Publication number
- NO306623B1 NO306623B1 NO901213A NO901213A NO306623B1 NO 306623 B1 NO306623 B1 NO 306623B1 NO 901213 A NO901213 A NO 901213A NO 901213 A NO901213 A NO 901213A NO 306623 B1 NO306623 B1 NO 306623B1
- Authority
- NO
- Norway
- Prior art keywords
- dna
- trna
- rna
- ribozyme
- producing
- Prior art date
Links
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims abstract description 22
- 108090000623 proteins and genes Proteins 0.000 title claims description 109
- 108020004414 DNA Proteins 0.000 title claims description 67
- 102000053602 DNA Human genes 0.000 title claims description 21
- 108091028043 Nucleic acid sequence Proteins 0.000 title claims description 19
- 238000002360 preparation method Methods 0.000 title description 8
- 108090000994 Catalytic RNA Proteins 0.000 claims abstract description 128
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims abstract description 111
- 108091092562 ribozyme Proteins 0.000 claims abstract description 109
- 102000053642 Catalytic RNA Human genes 0.000 claims abstract description 108
- 238000013518 transcription Methods 0.000 claims abstract description 37
- 230000035897 transcription Effects 0.000 claims abstract description 37
- 108020005544 Antisense RNA Proteins 0.000 claims abstract description 16
- 108020004566 Transfer RNA Proteins 0.000 claims description 102
- 210000004027 cell Anatomy 0.000 claims description 91
- 238000004519 manufacturing process Methods 0.000 claims description 21
- 239000003184 complementary RNA Substances 0.000 claims description 18
- 238000000338 in vitro Methods 0.000 claims description 18
- 108020005098 Anticodon Proteins 0.000 claims description 14
- 108700020796 Oncogene Proteins 0.000 claims description 12
- 108091034117 Oligonucleotide Proteins 0.000 claims description 11
- 238000003780 insertion Methods 0.000 claims description 6
- 230000037431 insertion Effects 0.000 claims description 6
- 102000043276 Oncogene Human genes 0.000 claims description 3
- 241000251131 Sphyrna Species 0.000 claims description 3
- 230000010261 cell growth Effects 0.000 claims description 3
- 108020000999 Viral RNA Proteins 0.000 claims description 2
- 230000024245 cell differentiation Effects 0.000 claims description 2
- 230000010837 receptor-mediated endocytosis Effects 0.000 claims description 2
- 244000309464 bull Species 0.000 claims 1
- 230000000536 complexating effect Effects 0.000 claims 1
- 210000003527 eukaryotic cell Anatomy 0.000 claims 1
- 230000000977 initiatory effect Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 26
- 230000002068 genetic effect Effects 0.000 abstract description 13
- 230000005764 inhibitory process Effects 0.000 abstract description 12
- 230000001965 increasing effect Effects 0.000 abstract description 8
- 230000008569 process Effects 0.000 abstract description 5
- 230000009467 reduction Effects 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 239000012581 transferrin Substances 0.000 description 35
- 210000000287 oocyte Anatomy 0.000 description 30
- 239000013612 plasmid Substances 0.000 description 27
- 102000004338 Transferrin Human genes 0.000 description 26
- 108090000901 Transferrin Proteins 0.000 description 26
- 238000003776 cleavage reaction Methods 0.000 description 26
- 230000007017 scission Effects 0.000 description 24
- 238000002474 experimental method Methods 0.000 description 23
- 229920000656 polylysine Polymers 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 239000012634 fragment Substances 0.000 description 18
- 108020004999 messenger RNA Proteins 0.000 description 17
- 239000002773 nucleotide Substances 0.000 description 17
- 125000003729 nucleotide group Chemical group 0.000 description 17
- 210000003924 normoblast Anatomy 0.000 description 16
- 241000287828 Gallus gallus Species 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 12
- 239000000499 gel Substances 0.000 description 12
- 230000032258 transport Effects 0.000 description 12
- 238000010276 construction Methods 0.000 description 11
- 102000039446 nucleic acids Human genes 0.000 description 11
- 108020004707 nucleic acids Proteins 0.000 description 11
- 150000007523 nucleic acids Chemical class 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 239000013598 vector Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 230000000295 complement effect Effects 0.000 description 10
- 238000011534 incubation Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 230000004069 differentiation Effects 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 8
- 108091092195 Intron Proteins 0.000 description 8
- 108010039918 Polylysine Proteins 0.000 description 8
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 8
- 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 8
- 230000008901 benefit Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 7
- 241000269370 Xenopus <genus> Species 0.000 description 7
- 238000010367 cloning Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 6
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 230000000692 anti-sense effect Effects 0.000 description 6
- 238000000376 autoradiography Methods 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000004202 carbamide Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 5
- 102000001554 Hemoglobins Human genes 0.000 description 5
- 108010054147 Hemoglobins Proteins 0.000 description 5
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 5
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 5
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 5
- 229920005654 Sephadex Polymers 0.000 description 5
- 239000012507 Sephadex™ Substances 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical compound C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 5
- 238000013507 mapping Methods 0.000 description 5
- 238000000520 microinjection Methods 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 230000002103 transcriptional effect Effects 0.000 description 5
- 241001430294 unidentified retrovirus Species 0.000 description 5
- 108020004491 Antisense DNA Proteins 0.000 description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 239000003816 antisense DNA Substances 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 210000000805 cytoplasm Anatomy 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 238000001502 gel electrophoresis Methods 0.000 description 4
- 230000035800 maturation Effects 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000007974 sodium acetate buffer Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 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 3
- 241000196324 Embryophyta Species 0.000 description 3
- 108010067770 Endopeptidase K Proteins 0.000 description 3
- 108060002716 Exonuclease Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 108010065868 RNA polymerase SP6 Proteins 0.000 description 3
- 102000004598 Small Nuclear Ribonucleoproteins Human genes 0.000 description 3
- 108010003165 Small Nuclear Ribonucleoproteins Proteins 0.000 description 3
- 241000269368 Xenopus laevis Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 102000013165 exonuclease Human genes 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000012064 sodium phosphate buffer Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 108091029536 tRNA precursor Proteins 0.000 description 3
- 230000001131 transforming effect Effects 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
- 108020005029 5' Flanking Region Proteins 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 108020004394 Complementary RNA Proteins 0.000 description 2
- 102000004594 DNA Polymerase I Human genes 0.000 description 2
- 108010017826 DNA Polymerase I Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 102000003951 Erythropoietin Human genes 0.000 description 2
- 108090000394 Erythropoietin Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 101150098499 III gene Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000007022 RNA scission Effects 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 108020005543 Satellite RNA Proteins 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 102000039471 Small Nuclear RNA Human genes 0.000 description 2
- 108020004688 Small Nuclear RNA Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 108700005078 Synthetic Genes Proteins 0.000 description 2
- 101710137500 T7 RNA polymerase Proteins 0.000 description 2
- 108010033576 Transferrin Receptors Proteins 0.000 description 2
- 239000007984 Tris EDTA buffer Substances 0.000 description 2
- 108091026823 U7 small nuclear RNA Proteins 0.000 description 2
- 101800005128 V-erbA oncogene Proteins 0.000 description 2
- 241001672648 Vieira Species 0.000 description 2
- 241000726445 Viroids Species 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 229940105423 erythropoietin Drugs 0.000 description 2
- 238000012869 ethanol precipitation Methods 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 239000003999 initiator Substances 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
- 230000003834 intracellular effect Effects 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- FFISLTWEISOMFC-UHFFFAOYSA-N pyridin-2-yl propanedithioate Chemical group CCC(=S)SC1=CC=CC=N1 FFISLTWEISOMFC-UHFFFAOYSA-N 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- -1 succinimidylpyridylthio propionate Chemical compound 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 108700008272 transferrin-polylysine conjugate Proteins 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- MEXAGTSTSPYCEP-JEDNCBNOSA-N (2s)-2,6-diaminohexanoic acid;hydrobromide Chemical compound Br.NCCCC[C@H](N)C(O)=O MEXAGTSTSPYCEP-JEDNCBNOSA-N 0.000 description 1
- IQFYYKKMVGJFEH-OFKYTIFKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(tritiooxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO[3H])O[C@H]1N1C(=O)NC(=O)C(C)=C1 IQFYYKKMVGJFEH-OFKYTIFKSA-N 0.000 description 1
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- YEMQNMTZLKJRHT-UHFFFAOYSA-N 2-(2,5-dioxopyrrolidin-1-yl)-2-pyridin-2-ylpropanethioic S-acid Chemical compound C=1C=CC=NC=1C(C)(C(S)=O)N1C(=O)CCC1=O YEMQNMTZLKJRHT-UHFFFAOYSA-N 0.000 description 1
- OSBLTNPMIGYQGY-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;boric acid Chemical compound OB(O)O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O OSBLTNPMIGYQGY-UHFFFAOYSA-N 0.000 description 1
- 108020005065 3' Flanking Region Proteins 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000711404 Avian avulavirus 1 Species 0.000 description 1
- 241000713840 Avian erythroblastosis virus Species 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 101150111062 C gene Proteins 0.000 description 1
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 1
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 1
- 108010026206 Conalbumin Proteins 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101100456896 Drosophila melanogaster metl gene Proteins 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108020004437 Endogenous Retroviruses Proteins 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241001131785 Escherichia coli HB101 Species 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 241000724709 Hepatitis delta virus Species 0.000 description 1
- 108020005350 Initiator Codon Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 239000007990 PIPES buffer Substances 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 108020004518 RNA Probes Proteins 0.000 description 1
- 239000003391 RNA probe Substances 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 239000008051 TBE buffer Substances 0.000 description 1
- 241000723677 Tobacco ringspot virus Species 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102000007238 Transferrin Receptors Human genes 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001295 alanines Chemical class 0.000 description 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000037429 base substitution Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 108091092330 cytoplasmic RNA Proteins 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000002074 deregulated effect Effects 0.000 description 1
- 230000029087 digestion 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
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- NPFOYSMITVOQOS-UHFFFAOYSA-K iron(III) citrate Chemical compound [Fe+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NPFOYSMITVOQOS-UHFFFAOYSA-K 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 230000008884 pinocytosis Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 208000009305 pseudorabies Diseases 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000011896 sensitive detection Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 108091029842 small nuclear ribonucleic acid Proteins 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 239000013603 viral vector Substances 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
-
- 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
-
- 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
- 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
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT60989 | 1989-03-16 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO901213D0 NO901213D0 (no) | 1990-03-15 |
| NO901213L NO901213L (no) | 1990-09-17 |
| NO306623B1 true NO306623B1 (no) | 1999-11-29 |
Family
ID=3495118
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO901213A NO306623B1 (no) | 1989-03-16 | 1990-03-15 | Fremgangsmåte for fremstilling av DNA-molekyl inneholdende deler av et gen som transkriberes av polymerase III og en DNA-sekvens som koder for et inhiberende RNA-molekyl |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0387775B1 (pt) |
| JP (1) | JP3330930B2 (pt) |
| KR (1) | KR900014591A (pt) |
| AT (1) | ATE140961T1 (pt) |
| AU (1) | AU637354B2 (pt) |
| CA (1) | CA2012312C (pt) |
| DD (1) | DD297838A5 (pt) |
| DE (1) | DE59010432D1 (pt) |
| DK (1) | DK0387775T3 (pt) |
| ES (1) | ES2090049T3 (pt) |
| FI (1) | FI105103B (pt) |
| GR (1) | GR3020935T3 (pt) |
| HU (2) | HU215187B (pt) |
| IE (1) | IE74850B1 (pt) |
| IL (1) | IL93754A (pt) |
| NO (1) | NO306623B1 (pt) |
| NZ (1) | NZ232917A (pt) |
| PT (1) | PT93440B (pt) |
| RU (1) | RU2136751C1 (pt) |
| ZA (1) | ZA901973B (pt) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04505261A (ja) * | 1989-05-10 | 1992-09-17 | スローン―ケツテリング・インステイテユート・フオー・キヤンサー・リサーチ | ポルｉｉｉプロモーターの制御下の転写可能な外来ｄｎａを含む安定的に形質転換された真核細胞 |
| DE4091533T (pt) * | 1989-08-31 | 1992-01-30 | ||
| JP2507895B2 (ja) * | 1989-12-19 | 1996-06-19 | 工業技術院長 | リボザイムの新規合成系 |
| WO1991019789A1 (en) * | 1990-06-19 | 1991-12-26 | Commonwealth Scientific And Industrial Research Organisation | Endonucleases |
| US6008343A (en) * | 1990-06-19 | 1999-12-28 | Gene Shears Pty. Ltd. | Nucleotide based endonucleases |
| ATE147098T1 (de) * | 1990-10-12 | 1997-01-15 | Max Planck Gesellschaft | Abgeänderte ribozyme |
| DE4104186A1 (de) * | 1991-02-12 | 1992-08-13 | Genentech Inc | Neue, ueber endozytose in hoehere eukaryotische zellen aufnehmbare, nukleinsaeure enthaltende komplexe |
| FR2687411A1 (fr) * | 1992-02-13 | 1993-08-20 | Nice Sophia Antipolis Universi | Vecteur comportant un gene viral transcrit par l'arn polymerase iii, et procede de production intracellulaire d'arn. |
| AU4259193A (en) * | 1992-04-28 | 1993-11-29 | Frank Andreas Harald Meyer | Medicament for the gene-therapeutic treatment of human beings, animals and plants, especially to block virus multiplication and carcinogenes and process for producing the medicament |
| WO1993023057A1 (en) * | 1992-05-14 | 1993-11-25 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for inhibiting cancer development |
| US5989906A (en) * | 1992-05-14 | 1999-11-23 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for inhibiting P-glycoprotein (mdr-1-gene) |
| US5610052A (en) * | 1992-08-26 | 1997-03-11 | Ribozyme Pharmaceuticals Inc. | Enzymatic RNA with activity to ras |
| CA2114312A1 (en) * | 1992-05-27 | 1993-12-09 | John J. Rossi | Chimeric trnalys-ribozyme molecules |
| US5827935A (en) * | 1992-05-27 | 1998-10-27 | City Of Hope | Chimeric tRNAlys -ribozyme molecules |
| EP0652705B1 (en) * | 1992-06-29 | 2005-12-14 | Gene Shears Pty Limited | Nucleic acids and methods of use thereof for controlling viral pathogens |
| WO1994013798A1 (en) * | 1992-12-16 | 1994-06-23 | Bergmann Johanna E | Agents for the prevention and treatment of human alzheimer's disease |
| DE69333216T2 (de) * | 1993-07-06 | 2004-06-24 | Université de Nice-Sophia Antipolis | Vektor, enthält ein bei ARN-Polymerase-III transcriptes Virus-Gen |
| US5837503A (en) * | 1993-07-07 | 1998-11-17 | Universite De Nice-Sophia-Antipolis | Vector containing viral gene transcribed by RNA polymerase III and methods for use |
| US5817635A (en) * | 1993-08-09 | 1998-10-06 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Modified ribozymes |
| AU692208B2 (en) * | 1994-01-24 | 1998-06-04 | City Of Hope | Inhibitors and target molecule co-localization |
| DE4424761C1 (de) * | 1994-07-04 | 1995-06-08 | Max Planck Gesellschaft | Expressionskassette für die Antisense- und die Ribozym-Expression |
| EP0837933A4 (en) | 1995-06-07 | 2003-05-21 | Commw Scient Ind Res Org | OPTIMIZED MINIZYMES AND MINIRIBOZYMES AND THE USE THEREOF |
| FR2755976B1 (fr) * | 1996-11-15 | 1999-01-15 | Idm Immuno Designed Molecules | Nouveaux complexes d'acides nucleiques et de polymere substitue par des residus entrainant la destabilisation des membranes cellulaires |
| US6057156A (en) * | 1997-01-31 | 2000-05-02 | Robozyme Pharmaceuticals, Inc. | Enzymatic nucleic acid treatment of diseases or conditions related to levels of epidermal growth factor receptors |
| AU1187099A (en) * | 1997-10-21 | 1999-05-10 | Ribozyme Pharmaceuticals, Inc. | Peptide bond formation using nucleic acid catalysts |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| AUPP249298A0 (en) | 1998-03-20 | 1998-04-23 | Ag-Gene Australia Limited | Synthetic genes and genetic constructs comprising same I |
| ES2374290T3 (es) | 1998-03-20 | 2012-02-15 | Commonwealth Scientific And Industrial Research Organisation | Genes sintéticos y constructos genéticos que comprenden los mismos. |
| CA2361201A1 (en) | 1999-01-28 | 2000-08-03 | Medical College Of Georgia Research Institute, Inc. | Composition and method for in vivo and in vitro attenuation of gene expression using double stranded rna |
| US6423885B1 (en) | 1999-08-13 | 2002-07-23 | Commonwealth Scientific And Industrial Research Organization (Csiro) | Methods for obtaining modified phenotypes in plant cells |
| US20020132257A1 (en) | 2001-01-31 | 2002-09-19 | Tony Giordano | Use of post-transcriptional gene silencing for identifying nucleic acid sequences that modulate the function of a cell |
| AUPR621501A0 (en) | 2001-07-06 | 2001-08-02 | Commonwealth Scientific And Industrial Research Organisation | Delivery of ds rna |
Family Cites Families (1)
| 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 |
-
1990
- 1990-03-13 DK DK90104701.9T patent/DK0387775T3/da active
- 1990-03-13 AT AT90104701T patent/ATE140961T1/de not_active IP Right Cessation
- 1990-03-13 DE DE59010432T patent/DE59010432D1/de not_active Expired - Lifetime
- 1990-03-13 ES ES90104701T patent/ES2090049T3/es not_active Expired - Lifetime
- 1990-03-13 EP EP90104701A patent/EP0387775B1/de not_active Expired - Lifetime
- 1990-03-14 NZ NZ232917A patent/NZ232917A/en unknown
- 1990-03-14 DD DD90338709A patent/DD297838A5/de not_active IP Right Cessation
- 1990-03-14 HU HU901584A patent/HU215187B/hu unknown
- 1990-03-15 CA CA002012312A patent/CA2012312C/en not_active Expired - Lifetime
- 1990-03-15 IL IL9375490A patent/IL93754A/en not_active IP Right Cessation
- 1990-03-15 IE IE93190A patent/IE74850B1/en not_active IP Right Cessation
- 1990-03-15 AU AU51301/90A patent/AU637354B2/en not_active Expired
- 1990-03-15 FI FI901296A patent/FI105103B/fi active IP Right Grant
- 1990-03-15 KR KR1019900003438A patent/KR900014591A/ko not_active Application Discontinuation
- 1990-03-15 ZA ZA901973A patent/ZA901973B/xx unknown
- 1990-03-15 NO NO901213A patent/NO306623B1/no not_active IP Right Cessation
- 1990-03-15 JP JP06549390A patent/JP3330930B2/ja not_active Expired - Lifetime
- 1990-03-15 PT PT93440A patent/PT93440B/pt not_active IP Right Cessation
- 1990-03-16 RU SU5010032A patent/RU2136751C1/ru active
-
1995
- 1995-06-30 HU HU95P/P00692P patent/HU211868A9/hu unknown
-
1996
- 1996-09-03 GR GR960402292T patent/GR3020935T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP3330930B2 (ja) | 2002-10-07 |
| KR900014591A (ko) | 1990-10-24 |
| HUT54206A (en) | 1991-01-28 |
| NO901213L (no) | 1990-09-17 |
| IE74850B1 (en) | 1997-08-13 |
| IL93754A (en) | 1995-12-31 |
| HU901584D0 (en) | 1990-06-28 |
| EP0387775B1 (de) | 1996-07-31 |
| PT93440B (pt) | 2001-07-31 |
| IL93754A0 (en) | 1990-12-23 |
| HU211868A9 (en) | 1995-12-28 |
| PT93440A (pt) | 1990-11-07 |
| CA2012312C (en) | 2001-08-14 |
| HU215187B (hu) | 1998-10-28 |
| ES2090049T3 (es) | 1996-10-16 |
| ZA901973B (en) | 1991-11-27 |
| JPH03130080A (ja) | 1991-06-03 |
| GR3020935T3 (en) | 1996-12-31 |
| AU637354B2 (en) | 1993-05-27 |
| CA2012312A1 (en) | 1990-09-16 |
| ATE140961T1 (de) | 1996-08-15 |
| FI105103B (fi) | 2000-06-15 |
| RU2136751C1 (ru) | 1999-09-10 |
| AU5130190A (en) | 1990-11-01 |
| IE900931L (en) | 1990-09-16 |
| DE59010432D1 (de) | 1996-09-05 |
| NZ232917A (en) | 1997-07-27 |
| DK0387775T3 (da) | 1996-11-04 |
| EP0387775A1 (de) | 1990-09-19 |
| NO901213D0 (no) | 1990-03-15 |
| DD297838A5 (de) | 1992-01-23 |
| FI901296A0 (fi) | 1990-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO306623B1 (no) | Fremgangsmåte for fremstilling av DNA-molekyl inneholdende deler av et gen som transkriberes av polymerase III og en DNA-sekvens som koder for et inhiberende RNA-molekyl | |
| CA2125974C (en) | Senescent cell derived inhibitors of dna synthesis | |
| US6458559B1 (en) | Multivalent RNA aptamers and their expression in multicellular organisms | |
| US6083744A (en) | DNA-armed ribozymes and minizymes | |
| KR100234840B1 (ko) | 트랜스-스플라이싱 리보자임을 이용한 세포절제 | |
| US5874414A (en) | Trans-splicing ribozymes | |
| US6852535B1 (en) | Polymerase III-based expression of therapeutic RNAS | |
| AU687001B2 (en) | Method and reagent for inhibiting cancer development | |
| Köhler et al. | Trans-splicing ribozymes for targeted gene delivery | |
| US20050142578A1 (en) | RNA interference mediated target discovery and target validation using short interfering nucleic acid (siNA) | |
| JPH10500309A (ja) | リボザイムを用いて再狭窄および癌を治療するための方法および組成物 | |
| Liu et al. | Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA | |
| US6183959B1 (en) | Method for target site selection and discovery | |
| JPH10507067A (ja) | テロメラーゼのｒｎａ成分 | |
| Ho et al. | Antisense oligonucleotides selectively regulate aspartyl β-hydroxylase and its truncated protein isoform in vitro but distribute poorly into A549 tumors in vivo | |
| US6830923B1 (en) | Genetics units for inhibiting the function of RNA | |
| AU2004205192A1 (en) | Production of ssDNA in vivo |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |