AU2004217437B2 - Use of antisense oligonucleotides or siRNA to suppress expression of eIF-5A1 - Google Patents
Use of antisense oligonucleotides or siRNA to suppress expression of eIF-5A1 Download PDFInfo
- Publication number
- AU2004217437B2 AU2004217437B2 AU2004217437A AU2004217437A AU2004217437B2 AU 2004217437 B2 AU2004217437 B2 AU 2004217437B2 AU 2004217437 A AU2004217437 A AU 2004217437A AU 2004217437 A AU2004217437 A AU 2004217437A AU 2004217437 B2 AU2004217437 B2 AU 2004217437B2
- Authority
- AU
- Australia
- Prior art keywords
- cells
- apoptosis
- seq
- expression
- sirna
- 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.)
- Ceased
Links
- 230000014509 gene expression Effects 0.000 title claims description 145
- 239000000074 antisense oligonucleotide Substances 0.000 title claims description 128
- 238000012230 antisense oligonucleotides Methods 0.000 title claims description 128
- 102100026761 Eukaryotic translation initiation factor 5A-1 Human genes 0.000 title claims description 19
- 101710126270 Eukaryotic translation initiation factor 5A-1 Proteins 0.000 title claims description 16
- 108020004459 Small interfering RNA Proteins 0.000 title claims description 14
- 108020000948 Antisense Oligonucleotides Proteins 0.000 title description 45
- 210000004027 cell Anatomy 0.000 claims description 625
- 230000006907 apoptotic process Effects 0.000 claims description 313
- 108091034117 Oligonucleotide Proteins 0.000 claims description 118
- 238000000034 method Methods 0.000 claims description 97
- 102000016614 Autophagy-Related Protein 5 Human genes 0.000 claims description 96
- 108010092776 Autophagy-Related Protein 5 Proteins 0.000 claims description 96
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 93
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 75
- 102000004127 Cytokines Human genes 0.000 claims description 55
- 108090000695 Cytokines Proteins 0.000 claims description 55
- 230000000692 anti-sense effect Effects 0.000 claims description 47
- 239000003795 chemical substances by application Substances 0.000 claims description 29
- 238000004519 manufacturing process Methods 0.000 claims description 26
- 210000003994 retinal ganglion cell Anatomy 0.000 claims description 26
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 20
- 230000002401 inhibitory effect Effects 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 18
- 102000000589 Interleukin-1 Human genes 0.000 claims description 16
- 108010002352 Interleukin-1 Proteins 0.000 claims description 16
- 230000004069 differentiation Effects 0.000 claims description 16
- 210000001616 monocyte Anatomy 0.000 claims description 16
- 230000030833 cell death Effects 0.000 claims description 15
- 230000000295 complement effect Effects 0.000 claims description 14
- 102000003810 Interleukin-18 Human genes 0.000 claims description 12
- 108090000171 Interleukin-18 Proteins 0.000 claims description 12
- 102000040430 polynucleotide Human genes 0.000 claims description 9
- 108091033319 polynucleotide Proteins 0.000 claims description 9
- 239000002157 polynucleotide Substances 0.000 claims description 9
- 230000000770 proinflammatory effect Effects 0.000 claims description 7
- 108090001005 Interleukin-6 Proteins 0.000 claims description 5
- 102000004889 Interleukin-6 Human genes 0.000 claims description 5
- 210000002919 epithelial cell Anatomy 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 description 108
- 241000700159 Rattus Species 0.000 description 106
- 239000012528 membrane Substances 0.000 description 86
- 102000004169 proteins and genes Human genes 0.000 description 84
- 235000018102 proteins Nutrition 0.000 description 81
- 108010074105 Factor Va Proteins 0.000 description 70
- 238000001890 transfection Methods 0.000 description 65
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 64
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 63
- 229940127093 camptothecin Drugs 0.000 description 63
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 63
- 239000002953 phosphate buffered saline Substances 0.000 description 59
- 238000011282 treatment Methods 0.000 description 58
- 239000002773 nucleotide Substances 0.000 description 54
- 125000003729 nucleotide group Chemical group 0.000 description 54
- 230000001640 apoptogenic effect Effects 0.000 description 53
- 238000002474 experimental method Methods 0.000 description 46
- 238000001262 western blot Methods 0.000 description 46
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 36
- 102000048231 Deoxyhypusine synthases Human genes 0.000 description 36
- 108700023218 Deoxyhypusine synthases Proteins 0.000 description 36
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 36
- 210000004940 nucleus Anatomy 0.000 description 36
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 35
- 210000004246 corpus luteum Anatomy 0.000 description 35
- 230000001965 increasing effect Effects 0.000 description 35
- 239000000203 mixture Substances 0.000 description 35
- 239000002299 complementary DNA Substances 0.000 description 34
- 239000000243 solution Substances 0.000 description 32
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 30
- 239000000523 sample Substances 0.000 description 30
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 28
- 206010028980 Neoplasm Diseases 0.000 description 28
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 28
- 230000000875 corresponding effect Effects 0.000 description 27
- 210000002966 serum Anatomy 0.000 description 27
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 26
- 238000013467 fragmentation Methods 0.000 description 26
- 238000006062 fragmentation reaction Methods 0.000 description 26
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- 238000001514 detection method Methods 0.000 description 25
- 210000005003 heart tissue Anatomy 0.000 description 25
- 238000011534 incubation Methods 0.000 description 25
- 239000007924 injection Substances 0.000 description 25
- 238000002347 injection Methods 0.000 description 25
- 108020004999 messenger RNA Proteins 0.000 description 25
- 210000001519 tissue Anatomy 0.000 description 25
- 239000013615 primer Substances 0.000 description 24
- 230000004044 response Effects 0.000 description 24
- 239000012634 fragment Substances 0.000 description 23
- 108090000765 processed proteins & peptides Proteins 0.000 description 23
- 125000003275 alpha amino acid group Chemical group 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 238000010240 RT-PCR analysis Methods 0.000 description 21
- 239000000834 fixative Substances 0.000 description 21
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- 238000002372 labelling Methods 0.000 description 19
- 108010085238 Actins Proteins 0.000 description 18
- 102000007469 Actins Human genes 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 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 18
- 238000010790 dilution Methods 0.000 description 18
- 239000012895 dilution Substances 0.000 description 18
- 239000002609 medium Substances 0.000 description 18
- 150000007523 nucleic acids Chemical class 0.000 description 18
- 102000004196 processed proteins & peptides Human genes 0.000 description 18
- 201000011510 cancer Diseases 0.000 description 17
- 230000006882 induction of apoptosis Effects 0.000 description 17
- 229920001184 polypeptide Polymers 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 16
- 208000010412 Glaucoma Diseases 0.000 description 16
- 235000001014 amino acid Nutrition 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 239000012737 fresh medium Substances 0.000 description 16
- 102000039446 nucleic acids Human genes 0.000 description 16
- 108020004707 nucleic acids Proteins 0.000 description 16
- 108010092160 Dactinomycin Proteins 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 15
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 15
- 229960000640 dactinomycin Drugs 0.000 description 15
- 239000000499 gel Substances 0.000 description 15
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 15
- 102000013415 peroxidase activity proteins Human genes 0.000 description 15
- 108040007629 peroxidase activity proteins Proteins 0.000 description 15
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 15
- 238000010186 staining Methods 0.000 description 15
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 14
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 14
- 108700020796 Oncogene Proteins 0.000 description 14
- 229920001213 Polysorbate 20 Polymers 0.000 description 14
- 239000004904 UV filter Substances 0.000 description 14
- 230000005775 apoptotic pathway Effects 0.000 description 14
- 229940098773 bovine serum albumin Drugs 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 208000028867 ischemia Diseases 0.000 description 14
- 235000013336 milk Nutrition 0.000 description 14
- 239000008267 milk Substances 0.000 description 14
- 210000004080 milk Anatomy 0.000 description 14
- 210000003733 optic disk Anatomy 0.000 description 14
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 14
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 14
- 229940063673 spermidine Drugs 0.000 description 14
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 13
- 102000001708 Protein Isoforms Human genes 0.000 description 13
- 108010029485 Protein Isoforms Proteins 0.000 description 13
- 150000001413 amino acids Chemical class 0.000 description 13
- 210000001130 astrocyte Anatomy 0.000 description 13
- 239000000872 buffer Substances 0.000 description 13
- 230000007423 decrease Effects 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 13
- 238000009396 hybridization Methods 0.000 description 13
- 102000014150 Interferons Human genes 0.000 description 12
- 108010050904 Interferons Proteins 0.000 description 12
- 230000001413 cellular effect Effects 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 229940079322 interferon Drugs 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- 101710154606 Hemagglutinin Proteins 0.000 description 11
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 11
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 11
- 239000002033 PVDF binder Substances 0.000 description 11
- 101710176177 Protein A56 Proteins 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 11
- 239000000185 hemagglutinin Substances 0.000 description 11
- 230000002062 proliferating effect Effects 0.000 description 11
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 11
- 230000014616 translation Effects 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 11
- 108020005345 3' Untranslated Regions Proteins 0.000 description 10
- 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 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
- 102000008070 Interferon-gamma Human genes 0.000 description 10
- 108010074328 Interferon-gamma Proteins 0.000 description 10
- 108090001007 Interleukin-8 Proteins 0.000 description 10
- 239000008367 deionised water Substances 0.000 description 10
- 229910021641 deionized water Inorganic materials 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 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 10
- 229960003130 interferon gamma Drugs 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 9
- 102000011727 Caspases Human genes 0.000 description 9
- 108010076667 Caspases Proteins 0.000 description 9
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 9
- 108091023040 Transcription factor Proteins 0.000 description 9
- 102000040945 Transcription factor Human genes 0.000 description 9
- 230000004913 activation Effects 0.000 description 9
- 230000027455 binding Effects 0.000 description 9
- 230000000903 blocking effect Effects 0.000 description 9
- 239000006167 equilibration buffer Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 230000003827 upregulation Effects 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 230000001464 adherent effect Effects 0.000 description 8
- 239000011543 agarose gel Substances 0.000 description 8
- 102000055102 bcl-2-Associated X Human genes 0.000 description 8
- 108700000707 bcl-2-Associated X Proteins 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000012636 effector Substances 0.000 description 8
- 108010085279 eukaryotic translation initiation factor 5A Proteins 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 210000002216 heart Anatomy 0.000 description 8
- 230000035772 mutation Effects 0.000 description 8
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 239000004017 serum-free culture medium Substances 0.000 description 8
- 235000020183 skimmed milk Nutrition 0.000 description 8
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 241000282320 Panthera leo Species 0.000 description 7
- 101001002417 Rattus norvegicus Eukaryotic translation initiation factor 5A-1 Proteins 0.000 description 7
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 7
- 239000013592 cell lysate Substances 0.000 description 7
- 238000010367 cloning Methods 0.000 description 7
- 238000006731 degradation reaction Methods 0.000 description 7
- 239000002158 endotoxin Substances 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 229920006008 lipopolysaccharide Polymers 0.000 description 7
- 210000004498 neuroglial cell Anatomy 0.000 description 7
- 239000008188 pellet Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000002207 retinal effect Effects 0.000 description 7
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 208000023275 Autoimmune disease Diseases 0.000 description 6
- 201000004569 Blindness Diseases 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- 102000016359 Fibronectins Human genes 0.000 description 6
- 108010067306 Fibronectins Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000012097 Lipofectamine 2000 Substances 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 6
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 6
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
- 238000000636 Northern blotting Methods 0.000 description 6
- 101710163270 Nuclease Proteins 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 6
- 231100000504 carcinogenesis Toxicity 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 238000010276 construction Methods 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 6
- 230000003619 fibrillary effect Effects 0.000 description 6
- 238000000799 fluorescence microscopy Methods 0.000 description 6
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 6
- 230000000877 morphologic effect Effects 0.000 description 6
- 239000012120 mounting media Substances 0.000 description 6
- 208000010125 myocardial infarction Diseases 0.000 description 6
- 210000001328 optic nerve Anatomy 0.000 description 6
- 210000001672 ovary Anatomy 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108091008146 restriction endonucleases Proteins 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 239000012192 staining solution Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 238000003146 transient transfection Methods 0.000 description 6
- 238000011144 upstream manufacturing Methods 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- 102100035793 CD83 antigen Human genes 0.000 description 5
- 241000283707 Capra Species 0.000 description 5
- 208000005623 Carcinogenesis Diseases 0.000 description 5
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 5
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 5
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 5
- 101001054354 Homo sapiens Eukaryotic translation initiation factor 5A-1 Proteins 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 239000004372 Polyvinyl alcohol Substances 0.000 description 5
- 238000002105 Southern blotting Methods 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 230000036952 cancer formation Effects 0.000 description 5
- 230000024245 cell differentiation Effects 0.000 description 5
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 5
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 5
- 230000034994 death Effects 0.000 description 5
- 230000007850 degeneration Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- BZUIJMCJNWUGKQ-BDAKNGLRSA-N hypusine Chemical compound NCC[C@@H](O)CNCCCC[C@H](N)C(O)=O BZUIJMCJNWUGKQ-BDAKNGLRSA-N 0.000 description 5
- 230000004410 intraocular pressure Effects 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 210000002540 macrophage Anatomy 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 229920002451 polyvinyl alcohol Polymers 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 238000000751 protein extraction Methods 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 230000001629 suppression Effects 0.000 description 5
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 5
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
- 102000000412 Annexin Human genes 0.000 description 4
- 108050008874 Annexin Proteins 0.000 description 4
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 4
- 102000008186 Collagen Human genes 0.000 description 4
- 208000011231 Crohn disease Diseases 0.000 description 4
- 241000287826 Gallus Species 0.000 description 4
- 208000003098 Ganglion Cysts Diseases 0.000 description 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 4
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical group N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 4
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 4
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 4
- 206010040047 Sepsis Diseases 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 208000005400 Synovial Cyst Diseases 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- 230000003367 anti-collagen effect Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 4
- 229920001436 collagen Polymers 0.000 description 4
- 230000002596 correlated effect Effects 0.000 description 4
- 210000000805 cytoplasm Anatomy 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 238000007865 diluting Methods 0.000 description 4
- 238000002565 electrocardiography Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 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 4
- 229960005542 ethidium bromide Drugs 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 230000002518 glial effect Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000000302 ischemic effect Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 239000012139 lysis buffer Substances 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 229940049954 penicillin Drugs 0.000 description 4
- 229920002401 polyacrylamide Polymers 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- 239000012096 transfection reagent Substances 0.000 description 4
- 230000005945 translocation Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 3
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 3
- 102000002241 Eukaryotic Initiation Factors Human genes 0.000 description 3
- 108010014863 Eukaryotic Initiation Factors Proteins 0.000 description 3
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 3
- 229930182566 Gentamicin Natural products 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 101000844963 Homo sapiens Deoxyhypusine synthase Proteins 0.000 description 3
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000024932 T cell mediated immunity Effects 0.000 description 3
- 108091036066 Three prime untranslated region Proteins 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 239000013504 Triton X-100 Substances 0.000 description 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000002424 anti-apoptotic effect Effects 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 238000010009 beating Methods 0.000 description 3
- 239000012148 binding buffer Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000004041 dendritic cell maturation Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000003828 downregulation Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 238000011067 equilibration Methods 0.000 description 3
- 238000007654 immersion Methods 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 102000044166 interleukin-18 binding protein Human genes 0.000 description 3
- 108010070145 interleukin-18 binding protein Proteins 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- HJRIWDYVYNNCFY-UHFFFAOYSA-M potassium;dimethylarsinate Chemical compound [K+].C[As](C)([O-])=O HJRIWDYVYNNCFY-UHFFFAOYSA-M 0.000 description 3
- 230000037452 priming Effects 0.000 description 3
- 230000000861 pro-apoptotic effect Effects 0.000 description 3
- 238000001243 protein synthesis Methods 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 108020004418 ribosomal RNA Proteins 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 101800000263 Acidic protein Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 102000012422 Collagen Type I Human genes 0.000 description 2
- 108010022452 Collagen Type I Proteins 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 101150013449 DHS gene Proteins 0.000 description 2
- 238000007399 DNA isolation Methods 0.000 description 2
- 239000003155 DNA primer Substances 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 108010067770 Endopeptidase K Proteins 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- -1 Hoescht 33258 Chemical class 0.000 description 2
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 240000004658 Medicago sativa Species 0.000 description 2
- 235000017587 Medicago sativa ssp. sativa Nutrition 0.000 description 2
- 241000711408 Murine respirovirus Species 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 108010069196 Neural Cell Adhesion Molecules Proteins 0.000 description 2
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 2
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 2
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 101710150344 Protein Rev Proteins 0.000 description 2
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 2
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 101100232702 Rattus norvegicus Eif5a gene Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 240000003768 Solanum lycopersicum Species 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 101710105083 Translation initiation factor 5A Proteins 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 2
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 108010067390 Viral Proteins Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- LEBBDRXHHNYZIA-LDUWYPJVSA-N [(2s,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] n-[(z)-1,3-dihydroxyoctadec-4-en-2-yl]carbamate Chemical compound CCCCCCCCCCCCC\C=C/C(O)C(CO)NC(=O)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O LEBBDRXHHNYZIA-LDUWYPJVSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 238000012867 alanine scanning Methods 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 230000003092 anti-cytokine Effects 0.000 description 2
- 230000001857 anti-mycotic effect Effects 0.000 description 2
- 239000002543 antimycotic Substances 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 230000001746 atrial effect Effects 0.000 description 2
- 230000008335 axon cargo transport Effects 0.000 description 2
- 102000055574 bcl-2 Homologous Antagonist-Killer Human genes 0.000 description 2
- 108700039689 bcl-2 Homologous Antagonist-Killer Proteins 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000012829 chemotherapy agent Substances 0.000 description 2
- 210000003837 chick embryo Anatomy 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 230000010428 chromatin condensation Effects 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 201000010897 colon adenocarcinoma Diseases 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 2
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 2
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- PGPFBXMCOQNMJO-VIFPVBQESA-N deoxyhypusine Chemical group NCCCCNCCCC[C@H](N)C(O)=O PGPFBXMCOQNMJO-VIFPVBQESA-N 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 235000013861 fat-free Nutrition 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 229940034998 human von willebrand factor Drugs 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 238000003125 immunofluorescent labeling Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000021995 interleukin-8 production Effects 0.000 description 2
- 230000005865 ionizing radiation Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 210000002596 lutein cell Anatomy 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 230000004983 pleiotropic effect Effects 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000001292 preischemic effect Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000002731 protein assay Methods 0.000 description 2
- 239000003531 protein hydrolysate Substances 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000010474 transient expression Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- NFKMCDNOKFCLOJ-UHFFFAOYSA-N (2-chloro-1H-indol-3-yl) dihydrogen phosphate Chemical compound C1=CC=C2C(OP(O)(=O)O)=C(Cl)NC2=C1 NFKMCDNOKFCLOJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 108090000672 Annexin A5 Proteins 0.000 description 1
- 102000004121 Annexin A5 Human genes 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- 208000036490 Arterial inflammations Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 102000004046 Caspase-2 Human genes 0.000 description 1
- 108090000552 Caspase-2 Proteins 0.000 description 1
- 108050005259 Caveolae-associated protein 2 Proteins 0.000 description 1
- 102100032231 Caveolae-associated protein 2 Human genes 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102100030497 Cytochrome c Human genes 0.000 description 1
- 108010075031 Cytochromes c Proteins 0.000 description 1
- 102000004594 DNA Polymerase I Human genes 0.000 description 1
- 108010017826 DNA Polymerase I Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 239000012594 Earle’s Balanced Salt Solution Substances 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 102100020987 Eukaryotic translation initiation factor 5 Human genes 0.000 description 1
- 101710204611 Eukaryotic translation initiation factor 5 Proteins 0.000 description 1
- 102100021002 Eukaryotic translation initiation factor 5A-2 Human genes 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000929319 Homo sapiens Actin, aortic smooth muscle Proteins 0.000 description 1
- 101000782195 Homo sapiens von Willebrand factor Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 101900102211 Human T-cell leukemia virus 1 Protein Rex Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000039996 IL-1 family Human genes 0.000 description 1
- 108091069196 IL-1 family Proteins 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 201000002287 Keratoconus Diseases 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000001940 Massive Hepatic Necrosis Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 101100325747 Mus musculus Bak1 gene Proteins 0.000 description 1
- 101001002432 Mus musculus Eukaryotic translation initiation factor 5A-1 Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 108091005461 Nucleic proteins Chemical group 0.000 description 1
- 208000023715 Ocular surface disease Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 235000014676 Phragmites communis Nutrition 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 1
- 208000032225 Proximal spinal muscular atrophy type 1 Diseases 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 229940122277 RNA polymerase inhibitor Drugs 0.000 description 1
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 1
- 108700020471 RNA-Binding Proteins Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 101000928655 Rattus norvegicus Deoxyhypusine synthase Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 101001010097 Shigella phage SfV Bactoprenol-linked glucose translocase Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 244000019194 Sorbus aucuparia Species 0.000 description 1
- 208000003954 Spinal Muscular Atrophies of Childhood Diseases 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 206010042573 Superovulation Diseases 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 241000255588 Tephritidae Species 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 208000024340 acute graft versus host disease Diseases 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000002022 anti-cellular effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000009925 apoptotic mechanism Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 101150024147 bax gene Proteins 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000011393 cytotoxic chemotherapy Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000005860 defense response to virus Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 102000006735 deoxyhypusine hydroxylase Human genes 0.000 description 1
- 108010028753 deoxyhypusine hydroxylase Proteins 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000003085 diluting agent Substances 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
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 108010045839 eIF-5A2 Proteins 0.000 description 1
- 101150074736 eif5a gene Proteins 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000002854 epidermolysis bullosa simplex superficialis Diseases 0.000 description 1
- 230000010502 episomal replication Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 description 1
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
- 230000010247 heart contraction Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000003118 histopathologic effect Effects 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000031037 interleukin-18 production Effects 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 239000013586 microbial product Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 230000003990 molecular pathway Effects 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000010309 neoplastic transformation Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000003959 neuroinflammation Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000001067 neuroprotector Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 1
- 230000030147 nuclear export Effects 0.000 description 1
- 210000004492 nuclear pore Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000005222 photoaffinity labeling Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 210000002729 polyribosome Anatomy 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- DZUXGQBLFALXCR-CDIPTNKSSA-N prostaglandin F1alpha Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1CCCCCCC(O)=O DZUXGQBLFALXCR-CDIPTNKSSA-N 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000021419 recognition of apoptotic cell Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 208000032253 retinal ischemia Diseases 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 235000006414 serbal de cazadores Nutrition 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000003584 silencer Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 102000055501 telomere Human genes 0.000 description 1
- 108091035539 telomere Proteins 0.000 description 1
- 210000003411 telomere Anatomy 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000025366 tissue development Effects 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 238000013042 tunel staining Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent 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
-
- 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
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- 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
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
-
- 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
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Ophthalmology & Optometry (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45167703P | 2003-03-05 | 2003-03-05 | |
| US60/451,677 | 2003-03-05 | ||
| US10/383,614 US7381708B2 (en) | 2001-07-23 | 2003-03-10 | Suppression of eIF5A1 expression by the use of antisense oligonucleotides for the prevention of retinal cell death in the glaucomatous eye |
| US10/383,614 | 2003-03-10 | ||
| US47619403P | 2003-06-06 | 2003-06-06 | |
| US60/476,194 | 2003-06-06 | ||
| US50473103P | 2003-09-22 | 2003-09-22 | |
| US60/504,731 | 2003-09-22 | ||
| US52824903P | 2003-12-10 | 2003-12-10 | |
| US60/528,249 | 2003-12-10 | ||
| PCT/US2004/006598 WO2004078940A2 (en) | 2003-03-05 | 2004-03-05 | USE OF ANTISENSE OLIGONUCLEOTIDES OR siRNA TO SUPPRESS EXPRESSION OF eIF-5A1 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2004217437A1 AU2004217437A1 (en) | 2004-09-16 |
| AU2004217437B2 true AU2004217437B2 (en) | 2009-11-19 |
Family
ID=32966688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2004217437A Ceased AU2004217437B2 (en) | 2003-03-05 | 2004-03-05 | Use of antisense oligonucleotides or siRNA to suppress expression of eIF-5A1 |
Country Status (9)
| Country | Link |
|---|---|
| US (5) | US20100168047A9 (enExample) |
| EP (1) | EP1601767B1 (enExample) |
| JP (1) | JP2006520611A (enExample) |
| KR (1) | KR20050098954A (enExample) |
| AU (1) | AU2004217437B2 (enExample) |
| CA (1) | CA2517974A1 (enExample) |
| NZ (1) | NZ542665A (enExample) |
| TW (1) | TW200427695A (enExample) |
| WO (1) | WO2004078940A2 (enExample) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7381708B2 (en) | 2001-07-23 | 2008-06-03 | Sensco Technologies, Inc. | Suppression of eIF5A1 expression by the use of antisense oligonucleotides for the prevention of retinal cell death in the glaucomatous eye |
| JP2006520611A (ja) * | 2003-03-05 | 2006-09-14 | セネスコ テクノロジーズ，インコーポレイティド | ｅＩＦ−５Ａ１の発現を抑制するための、アンチセンス・オリゴヌクレオチド又はｓｉＲＮＡの使用 |
| CN101014708B (zh) * | 2003-03-05 | 2011-11-02 | 森尼斯科技术公司 | 反义寡核苷酸或siRNA在抑制eIF-5A1表达中的应用 |
| NZ574973A (en) * | 2003-06-06 | 2010-10-29 | Senesco Technologies Inc | Inhibition of apoptosis-specific eIF-5A ("eIF-5A1") with antisense oligonucleotides and siRNAs as anti-inflammatory therapeutics |
| US20140371299A1 (en) * | 2004-06-07 | 2014-12-18 | Senesco Technologies, Inc. | Use of Apoptosis-Specific elF-5A siRNA to Down Regulate Expression of Proinflammatory Cytokines to Treat Sepsis |
| JP2008507278A (ja) * | 2004-07-20 | 2008-03-13 | セネスコ テクノロジーズ，インコーポレイティド | 炎症反応を阻害／抑制するためのアポトーシス特異的ｅＩＦ−５Ａ・ｓｉＲＮＡ及びアンチセンスポリヌクレオチドの使用 |
| EP1828383A2 (en) * | 2004-12-03 | 2007-09-05 | Senesco Technologies, Inc. | Apoptosis-specific eif-5a and polynucleotides encoding same |
| JP5205058B2 (ja) * | 2004-12-03 | 2013-06-05 | セネスコ テクノロジーズ，インコーポレイティド | 種子の収量を増大させる方法 |
| KR20080009048A (ko) | 2005-01-25 | 2008-01-24 | 프롤렉시스 파마슈티칼스, 인크. | 항종양제로서 퀴녹살린 유도체 |
| DE102005005528A1 (de) * | 2005-01-30 | 2006-08-03 | Eberhard-Karls-Universität Tübingen Universitätsklinikum | Injizierbares Mittel zur zielgerichteten Behandlung von retinalen Ganglienzellen |
| US8105611B2 (en) * | 2005-06-17 | 2012-01-31 | Allergan, Inc. | Treatment of autoimmune disorder with a neurotoxin |
| CA2633043A1 (en) * | 2005-12-13 | 2007-06-21 | Senesco Technologies, Inc. | Use of eif-5a to kill multiple myeloma cells |
| EP1996706A2 (en) * | 2006-03-20 | 2008-12-03 | Senesco Technologies, Inc. | Use of apoptosis-specific eif-5a sirna to down regulate expression of proinflammatory cytokines to treat sepsis |
| WO2007109677A2 (en) * | 2006-03-20 | 2007-09-27 | Senesco Technologies, Inc. | A novel method of protecting islet cells from apoptosis during the donor harvesting process |
| WO2007115047A2 (en) * | 2006-03-29 | 2007-10-11 | Senesco Technologies, Inc. | Inhibition of hiv replication and expression of p24 with eif-5a |
| EP2078079B1 (en) | 2006-11-01 | 2011-05-04 | The Medical Research and Infrastructure Fund of the Tel-Aviv Sourasky Medical Center | Adipocyte-specific constructs and methods for inhibiting platelet-type 12 lipoxygenase expression |
| WO2008065429A1 (en) * | 2006-11-30 | 2008-06-05 | Ucl Business Plc | Method for delivering gene therapy vectors to the optic nerve head |
| CN101126098B (zh) * | 2007-07-05 | 2012-07-11 | 深圳市第二人民医院 | 特异性抑制gfap蛋白表达的小干扰rna分子表达载体及其构建方法与用途 |
| WO2009114487A2 (en) | 2008-03-07 | 2009-09-17 | Senesco Technologies, Inc. | Use of sirna to achieve down regulation of an endogenous gene in combination with the use of a sense construct to achieve expression of a desired polynucleotide |
| JP5578522B2 (ja) | 2008-05-27 | 2014-08-27 | 義規 世古 | アポトーシス誘導薬 |
| US8946239B2 (en) | 2008-07-10 | 2015-02-03 | Duquesne University Of The Holy Spirit | Substituted pyrrolo, -furano, and cyclopentylpyrimidines having antimitotic and/or antitumor activity and methods of use thereof |
| US8445638B2 (en) | 2008-09-03 | 2013-05-21 | Senesco Technologies, Inc. | Use of a truncated eIF-5A1 polynucleotide to induce apoptosis in cancer cells |
| AU2009308380B2 (en) * | 2008-10-22 | 2015-05-28 | Suzhou Ribo Life Science Co., Ltd. | Methods for treating eye disorders |
| US20120196918A1 (en) * | 2009-04-08 | 2012-08-02 | Mirmira Raghavendra G | PREVENTING ISLET INFLAMMATION AND DYSFUNCTION AND MAINTAINING PROPER GLUCOSE LEVELS BY CONTROLLING eIF5A AND ITS HYPUSINATION |
| DK3338765T3 (en) | 2009-12-01 | 2019-03-04 | Translate Bio Inc | STEROID DERIVATIVE FOR THE SUPPLY OF MRNA IN HUMANGENETIC DISEASES |
| JP6184945B2 (ja) | 2011-06-08 | 2017-08-23 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | ｍＲＮＡ送達のための脂質ナノ粒子組成物および方法 |
| EP3536787A1 (en) | 2012-06-08 | 2019-09-11 | Translate Bio, Inc. | Nuclease resistant polynucleotides and uses thereof |
| JP6586075B2 (ja) | 2013-03-14 | 2019-10-02 | トランスレイト バイオ， インコーポレイテッド | メッセンジャーｒｎａの精製方法 |
| IL305374A (en) | 2013-03-14 | 2023-10-01 | Ethris Gmbh | Cftr mrna compositions and related methods and uses |
| JP2016516804A (ja) | 2013-04-17 | 2016-06-09 | ファイザー・インク | 心血管疾患を治療するためのｎ−ピペリジン−３−イルベンズアミド誘導体 |
| CN103421791B (zh) * | 2013-06-24 | 2015-04-15 | 广西医科大学 | 一种抑制人-单核巨噬细胞TLR2表达的siRNA及其应用 |
| EA034103B1 (ru) | 2013-10-22 | 2019-12-27 | Транслейт Био, Инк. | СПОСОБ ЛЕЧЕНИЯ ФЕНИЛКЕТОНУРИИ С ПРИМЕНЕНИЕМ мРНК |
| BR112016009014B1 (pt) | 2013-10-22 | 2024-02-06 | Translate Bio, Inc | USO DE COMPOSIÇÃO COMPREENDENDO mRNA PARA DEFICIÊNCIA DE ARGININOSSUCINATO SINTETASE |
| MX373952B (es) | 2014-04-25 | 2020-07-13 | Shire Human Genetic Therapies | Métodos de purificación de arn mensajero. |
| EP3585417B1 (en) | 2017-02-27 | 2023-02-22 | Translate Bio, Inc. | Method of making a codon-optimized cftr mrna |
| EP3624824B1 (en) | 2017-05-16 | 2024-07-10 | Translate Bio, Inc. | Codon-optimized mrna encoding cftr for use in treating cystic fibrosis |
| US11865182B2 (en) | 2017-11-18 | 2024-01-09 | Nzola DE MAGALHAES | Product and process for employing GC7 (N1-guanyl-1,7-diaminoheptane) based antigen binding conjugates in cancer therapy |
| CA3108544A1 (en) | 2018-08-24 | 2020-02-27 | Translate Bio, Inc. | Methods for purification of messenger rna |
| AU2019384557B2 (en) | 2018-11-21 | 2025-07-17 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of nebulized mRNA encoding CFTR |
| CN114231551B (zh) * | 2021-12-24 | 2023-09-29 | 云南大学 | 蛋白在促进昆虫淋巴细胞凋亡和/或防治害虫中的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003010886A1 (fr) * | 2001-07-23 | 2003-02-06 | Niigata Seimitsu Co., Ltd. | Circuit d'amplification |
| AU2003234482A1 (en) * | 2002-05-07 | 2003-11-11 | Senesco Technologies, Inc. | Nucleic acids, polypeptides, and methods for modulating apoptosis |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1173897A (zh) | 1995-02-13 | 1998-02-18 | 诺瓦蒂斯有限公司 | 真核起始因子5A(eIF－5A)突变体 |
| ATE294583T1 (de) * | 1996-09-13 | 2005-05-15 | Univ Florida | Verfahren zur hemmung von eif5a-biosynthese |
| US6448040B1 (en) | 1997-06-20 | 2002-09-10 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibitor of cellular proliferation |
| US6506559B1 (en) * | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| US7358418B2 (en) | 1999-07-06 | 2008-04-15 | Senesco Technologies, Inc. | Isoforms of eIF-5A: senescence-induced eLF5A; wounding-induced eIF-4A; growth eIF-5A; and DHS |
| CA2376065A1 (en) | 1999-08-06 | 2001-02-15 | Pharmacia & Upjohn Company | Crystallization and structure determination of staphylococcus aureus elongation factor p |
| DK2796553T3 (da) * | 2000-03-30 | 2019-09-30 | Whitehead Inst Biomedical Res | Rna-sekvensspecifikke formidlere af rna-interferens |
| CZ302719B6 (cs) * | 2000-12-01 | 2011-09-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Izolovaná molekula dvouretezcové RNA, zpusob její výroby a její použití |
| US7381708B2 (en) * | 2001-07-23 | 2008-06-03 | Sensco Technologies, Inc. | Suppression of eIF5A1 expression by the use of antisense oligonucleotides for the prevention of retinal cell death in the glaucomatous eye |
| US7217517B2 (en) * | 2001-07-23 | 2007-05-15 | Senesco Technologies, Inc. | Nucleic acids, polypeptides, and methods for modulating apoptosis |
| US7166467B2 (en) * | 2001-07-23 | 2007-01-23 | Senesco Technologies, Inc. | Nucleic acids, polypeptides, compositions, and methods for modulating apoptosis |
| WO2003016572A1 (en) * | 2001-08-17 | 2003-02-27 | Eli Lilly And Company | Oligonucleotide therapeutics for treating hepatitis c virus infections |
| EP1572902B1 (en) * | 2002-02-01 | 2014-06-11 | Life Technologies Corporation | HIGH POTENCY siRNAS FOR REDUCING THE EXPRESSION OF TARGET GENES |
| EP1560931B1 (en) * | 2002-11-14 | 2011-07-27 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
| JP2006520611A (ja) * | 2003-03-05 | 2006-09-14 | セネスコ テクノロジーズ，インコーポレイティド | ｅＩＦ−５Ａ１の発現を抑制するための、アンチセンス・オリゴヌクレオチド又はｓｉＲＮＡの使用 |
| NZ574973A (en) | 2003-06-06 | 2010-10-29 | Senesco Technologies Inc | Inhibition of apoptosis-specific eIF-5A ("eIF-5A1") with antisense oligonucleotides and siRNAs as anti-inflammatory therapeutics |
-
2004
- 2004-03-05 JP JP2006509126A patent/JP2006520611A/ja active Pending
- 2004-03-05 CA CA002517974A patent/CA2517974A1/en not_active Abandoned
- 2004-03-05 NZ NZ542665A patent/NZ542665A/en unknown
- 2004-03-05 EP EP04717933A patent/EP1601767B1/en not_active Expired - Lifetime
- 2004-03-05 AU AU2004217437A patent/AU2004217437B2/en not_active Ceased
- 2004-03-05 WO PCT/US2004/006598 patent/WO2004078940A2/en not_active Ceased
- 2004-03-05 TW TW093105908A patent/TW200427695A/zh unknown
- 2004-03-05 KR KR1020057015276A patent/KR20050098954A/ko not_active Ceased
-
2005
- 2005-05-23 US US11/134,445 patent/US20100168047A9/en not_active Abandoned
- 2005-11-28 US US11/287,460 patent/US7662796B2/en not_active Expired - Fee Related
-
2009
- 2009-12-17 US US12/640,148 patent/US8242256B2/en not_active Expired - Fee Related
-
2011
- 2011-05-02 US US13/099,171 patent/US8754057B2/en not_active Expired - Fee Related
-
2012
- 2012-08-10 US US13/572,123 patent/US20130066058A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003010886A1 (fr) * | 2001-07-23 | 2003-02-06 | Niigata Seimitsu Co., Ltd. | Circuit d'amplification |
| AU2003234482A1 (en) * | 2002-05-07 | 2003-11-11 | Senesco Technologies, Inc. | Nucleic acids, polypeptides, and methods for modulating apoptosis |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004078940A2 (en) | 2004-09-16 |
| JP2006520611A (ja) | 2006-09-14 |
| US20060094677A1 (en) | 2006-05-04 |
| EP1601767B1 (en) | 2012-04-25 |
| CA2517974A1 (en) | 2004-09-16 |
| AU2004217437A1 (en) | 2004-09-16 |
| US20060178330A1 (en) | 2006-08-10 |
| KR20050098954A (ko) | 2005-10-12 |
| NZ542665A (en) | 2008-05-30 |
| US20110098460A1 (en) | 2011-04-28 |
| US8242256B2 (en) | 2012-08-14 |
| TW200427695A (en) | 2004-12-16 |
| US7662796B2 (en) | 2010-02-16 |
| US20130066058A1 (en) | 2013-03-14 |
| WO2004078940A8 (en) | 2005-10-27 |
| US8754057B2 (en) | 2014-06-17 |
| US20120129910A1 (en) | 2012-05-24 |
| WO2004078940A3 (en) | 2004-12-16 |
| EP1601767A2 (en) | 2005-12-07 |
| US20100168047A9 (en) | 2010-07-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2004217437B2 (en) | Use of antisense oligonucleotides or siRNA to suppress expression of eIF-5A1 | |
| AU2004258070B2 (en) | Inhibition of apoptosis-specific elF-5A ("elF-5A1") with antisense oligonucleotides and siRNAs as anti-inflammatory therapeutics | |
| JP5566250B2 (ja) | ｅＩＦ−５Ａ１の発現を抑制するための、アンチセンス・オリゴヌクレオチド又はｓｉＲＮＡの使用 | |
| AU2005269647B2 (en) | Use of apoptosis-specific eIF-5A siRNAs and antisense polynucleotides to inhibit/suppress an inflammatory response | |
| EP1959010A2 (en) | Apoptosis-specific eif-5A and polynucleotides encoding same | |
| US20060287265A1 (en) | Apoptosis-specific eIF-5A and polynucleotides encoding same | |
| KR20070018146A (ko) | 염증 반응을 저해/억제하기 위한 아폽토시스-특이적ｅＩＦ-5Ａ ｓｉＲＮＡ 및 안티센스 폴리뉴클레오타이드의이용 | |
| HK1110889A (en) | Use of apoptosis-specific eif-5a sirnas and antisense polynucleotides to inhibit/suppress an inflammatory response | |
| HK1107369A (en) | Use of antisense oligonucleotides or sirna to suppress expression of eif-5a1 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| DA2 | Applications for amendment section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE NAME OF THE INVENTOR TO ADD CO-INVENTORS CLICHE, DOMINIC;HEIKKILA, ELISABETH MARGARET; SENCHYNA, DIANE MICHELLE AND FLANAGAN, JOHN GERARD. |
|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE NAME OF THE INVENTOR TO ADD CO-INVENTORS CLICHE, DOMINIC;HEIKKILA, ELISABETH MARGARET; SENCHYNA, DIANE MICHELLE AND FLANAGAN, JOHN GERARD |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |