JP2021003106A - アルブミン産生及び細胞増殖 - Google Patents
アルブミン産生及び細胞増殖 Download PDFInfo
- Publication number
- JP2021003106A JP2021003106A JP2020126934A JP2020126934A JP2021003106A JP 2021003106 A JP2021003106 A JP 2021003106A JP 2020126934 A JP2020126934 A JP 2020126934A JP 2020126934 A JP2020126934 A JP 2020126934A JP 2021003106 A JP2021003106 A JP 2021003106A
- Authority
- JP
- Japan
- Prior art keywords
- short
- rna
- albumin
- cells
- cell
- 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.)
- Granted
Links
- 108010088751 Albumins Proteins 0.000 title claims abstract description 236
- 102000009027 Albumins Human genes 0.000 title claims abstract description 228
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 84
- 230000004663 cell proliferation Effects 0.000 title description 48
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 154
- 102100034808 CCAAT/enhancer-binding protein alpha Human genes 0.000 claims abstract description 43
- 101000945515 Homo sapiens CCAAT/enhancer-binding protein alpha Proteins 0.000 claims abstract description 43
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 208000035475 disorder Diseases 0.000 claims abstract description 28
- 208000003623 Hypoalbuminemia Diseases 0.000 claims abstract description 22
- 230000003213 activating effect Effects 0.000 claims abstract description 8
- 230000002265 prevention Effects 0.000 claims abstract description 8
- 206010030113 Oedema Diseases 0.000 claims abstract description 5
- 208000006454 hepatitis Diseases 0.000 claims abstract description 5
- 231100000283 hepatitis Toxicity 0.000 claims abstract description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 301
- 210000004027 cell Anatomy 0.000 claims description 241
- 238000000034 method Methods 0.000 claims description 166
- 239000002773 nucleotide Substances 0.000 claims description 66
- 125000003729 nucleotide group Chemical group 0.000 claims description 66
- 230000014509 gene expression Effects 0.000 claims description 50
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 47
- 108700009124 Transcription Initiation Site Proteins 0.000 claims description 45
- 238000011282 treatment Methods 0.000 claims description 35
- 208000014018 liver neoplasm Diseases 0.000 claims description 22
- 201000007270 liver cancer Diseases 0.000 claims description 21
- 230000000295 complement effect Effects 0.000 claims description 20
- 238000011144 upstream manufacturing Methods 0.000 claims description 19
- 238000000338 in vitro Methods 0.000 claims description 18
- 238000013461 design Methods 0.000 claims description 17
- 108091026890 Coding region Proteins 0.000 claims description 15
- 230000010261 cell growth Effects 0.000 claims description 14
- 210000000130 stem cell Anatomy 0.000 claims description 13
- 108091033380 Coding strand Proteins 0.000 claims description 12
- 238000003860 storage Methods 0.000 claims description 12
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 10
- 230000002062 proliferating effect Effects 0.000 claims description 9
- 230000002411 adverse Effects 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 6
- 208000012868 Overgrowth Diseases 0.000 claims description 5
- 230000004044 response Effects 0.000 claims description 5
- 238000003745 diagnosis Methods 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract description 18
- 206010028980 Neoplasm Diseases 0.000 description 53
- 108020004999 messenger RNA Proteins 0.000 description 44
- 108091029810 SaRNA Proteins 0.000 description 43
- 230000000692 anti-sense effect Effects 0.000 description 37
- 210000004185 liver Anatomy 0.000 description 33
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 32
- 102000004196 processed proteins & peptides Human genes 0.000 description 31
- 108090000765 processed proteins & peptides Proteins 0.000 description 31
- 108020004459 Small interfering RNA Proteins 0.000 description 29
- 229920001184 polypeptide Polymers 0.000 description 29
- 238000001890 transfection Methods 0.000 description 25
- 210000003494 hepatocyte Anatomy 0.000 description 24
- 150000007523 nucleic acids Chemical class 0.000 description 23
- 230000007246 mechanism Effects 0.000 description 22
- 201000011510 cancer Diseases 0.000 description 21
- 230000003827 upregulation Effects 0.000 description 21
- 241000700159 Rattus Species 0.000 description 20
- 102000004169 proteins and genes Human genes 0.000 description 18
- 108091034117 Oligonucleotide Proteins 0.000 description 17
- 230000035755 proliferation Effects 0.000 description 17
- 235000018102 proteins Nutrition 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 230000012010 growth Effects 0.000 description 15
- 210000004962 mammalian cell Anatomy 0.000 description 15
- 102000039446 nucleic acids Human genes 0.000 description 15
- 108020004707 nucleic acids Proteins 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 14
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 230000009368 gene silencing by RNA Effects 0.000 description 13
- 239000002502 liposome Substances 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- 239000004055 small Interfering RNA Substances 0.000 description 13
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 230000035897 transcription Effects 0.000 description 13
- 238000013518 transcription Methods 0.000 description 13
- 238000002965 ELISA Methods 0.000 description 12
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 12
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 238000002512 chemotherapy Methods 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 238000010586 diagram Methods 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 10
- 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 10
- 238000011374 additional therapy Methods 0.000 description 10
- 239000000412 dendrimer Substances 0.000 description 10
- 229920000736 dendritic polymer Polymers 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 230000003908 liver function Effects 0.000 description 10
- 108020005544 Antisense RNA Proteins 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 102000040945 Transcription factor Human genes 0.000 description 9
- 108091023040 Transcription factor Proteins 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000003828 downregulation Effects 0.000 description 9
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 9
- 230000001105 regulatory effect Effects 0.000 description 9
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 8
- 108010082126 Alanine transaminase Proteins 0.000 description 8
- 108010086524 Hepatocyte Nuclear Factor 4 Proteins 0.000 description 8
- 238000001516 cell proliferation assay Methods 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 210000002919 epithelial cell Anatomy 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 230000007017 scission Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 108091023037 Aptamer Proteins 0.000 description 7
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 7
- 206010016654 Fibrosis Diseases 0.000 description 7
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 7
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 7
- 238000010240 RT-PCR analysis Methods 0.000 description 7
- 238000004422 calculation algorithm Methods 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 208000019423 liver disease Diseases 0.000 description 7
- 230000005030 transcription termination Effects 0.000 description 7
- 230000014616 translation Effects 0.000 description 7
- 230000005748 tumor development Effects 0.000 description 7
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 6
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 6
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 6
- 108091006905 Human Serum Albumin Proteins 0.000 description 6
- 102000008100 Human Serum Albumin Human genes 0.000 description 6
- 206010060862 Prostate cancer Diseases 0.000 description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 6
- 238000011529 RT qPCR Methods 0.000 description 6
- 108010071390 Serum Albumin Proteins 0.000 description 6
- 102000007562 Serum Albumin Human genes 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000007882 cirrhosis Effects 0.000 description 6
- 239000003184 complementary RNA Substances 0.000 description 6
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 125000003831 tetrazolyl group Chemical group 0.000 description 6
- 230000004614 tumor growth Effects 0.000 description 6
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 5
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 5
- 102000015902 Hepatocyte nuclear factor 4-alpha Human genes 0.000 description 5
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 238000002591 computed tomography Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 4
- 108020004417 Untranslated RNA Proteins 0.000 description 4
- 102000039634 Untranslated RNA Human genes 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- WRUAHXANJKHFIL-UHFFFAOYSA-L benzene-1,3-disulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC(S([O-])(=O)=O)=C1 WRUAHXANJKHFIL-UHFFFAOYSA-L 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 238000007449 liver function test Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 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 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 102000000905 Cadherin Human genes 0.000 description 3
- 108050007957 Cadherin Proteins 0.000 description 3
- 101710107035 Gamma-glutamyltranspeptidase Proteins 0.000 description 3
- 101710173228 Glutathione hydrolase proenzyme Proteins 0.000 description 3
- 206010019695 Hepatic neoplasm Diseases 0.000 description 3
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 3
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 3
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 201000000053 blastoma Diseases 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 230000002222 downregulating effect Effects 0.000 description 3
- 201000008184 embryoma Diseases 0.000 description 3
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 238000002595 magnetic resonance imaging Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 231100000572 poisoning Toxicity 0.000 description 3
- 230000000607 poisoning effect Effects 0.000 description 3
- 238000004445 quantitative analysis Methods 0.000 description 3
- 238000007674 radiofrequency ablation Methods 0.000 description 3
- 238000010839 reverse transcription Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 3
- 239000003981 vehicle Substances 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
- 208000022309 Alcoholic Liver disease Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- -1 C / EBP-β Proteins 0.000 description 2
- 108010064535 CCAAT-Enhancer-Binding Protein-beta Proteins 0.000 description 2
- 102000015280 CCAAT-Enhancer-Binding Protein-beta Human genes 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 101150061453 Cebpa gene Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010077544 Chromatin Proteins 0.000 description 2
- 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 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 108010086512 Hepatocyte Nuclear Factor 1 Proteins 0.000 description 2
- 102000006754 Hepatocyte Nuclear Factor 1 Human genes 0.000 description 2
- 101150068639 Hnf4a gene Proteins 0.000 description 2
- 101000891649 Homo sapiens Transcription elongation factor A protein-like 1 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 101000930477 Mus musculus Albumin Proteins 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound 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 2
- 108010079855 Peptide Aptamers Proteins 0.000 description 2
- 102000012425 Polycomb-Group Proteins Human genes 0.000 description 2
- 108010022429 Polycomb-Group Proteins Proteins 0.000 description 2
- 108010039918 Polylysine Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 108091008103 RNA aptamers Proteins 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 230000004570 RNA-binding Effects 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 108091081021 Sense strand Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000010317 ablation therapy Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000011394 anticancer treatment Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000000712 assembly Effects 0.000 description 2
- 238000000429 assembly Methods 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- OQUUTERJWTYTHP-UHFFFAOYSA-N butanedioate;1h-tetrazol-1-ium Chemical compound [NH2+]1C=NN=N1.[NH2+]1C=NN=N1.[O-]C(=O)CCC([O-])=O OQUUTERJWTYTHP-UHFFFAOYSA-N 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000003483 chromatin Anatomy 0.000 description 2
- 238000007398 colorimetric assay Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000012938 design process Methods 0.000 description 2
- 238000001784 detoxification Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000000763 evoking effect Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 208000010706 fatty liver disease Diseases 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 230000009437 off-target effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920000962 poly(amidoamine) Polymers 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 210000005267 prostate cell Anatomy 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 229920002477 rna polymer Polymers 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 102000008682 Argonaute Proteins Human genes 0.000 description 1
- 108010088141 Argonaute Proteins Proteins 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101710168309 CCAAT/enhancer-binding protein alpha Proteins 0.000 description 1
- 101710134031 CCAAT/enhancer-binding protein beta Proteins 0.000 description 1
- 102100034798 CCAAT/enhancer-binding protein beta Human genes 0.000 description 1
- 108091007914 CDKs Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 101710150820 Cellular tumor antigen p53 Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 108020004394 Complementary RNA Proteins 0.000 description 1
- 102100026398 Cyclic AMP-responsive element-binding protein 3 Human genes 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000003849 Cytochrome P450 Human genes 0.000 description 1
- 101710199286 Cytosol aminopeptidase Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108091008102 DNA aptamers Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 101710197780 E3 ubiquitin-protein ligase LAP Proteins 0.000 description 1
- 102000039106 EBP family Human genes 0.000 description 1
- 108091065819 EBP family Proteins 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000701533 Escherichia virus T4 Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 235000014751 Gossypium arboreum Nutrition 0.000 description 1
- 101800000194 Growth hormone-binding protein Proteins 0.000 description 1
- 102400001066 Growth hormone-binding protein Human genes 0.000 description 1
- 108020005004 Guide RNA Proteins 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 102100022054 Hepatocyte nuclear factor 4-alpha Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000855520 Homo sapiens Cyclic AMP-responsive element-binding protein 3 Proteins 0.000 description 1
- 101001045740 Homo sapiens Hepatocyte nuclear factor 4-alpha Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 241000218069 Kokia Species 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 101710204480 Lysosomal acid phosphatase Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000596402 Mus musculus Neuronal vesicle trafficking-associated protein 1 Proteins 0.000 description 1
- 101000800539 Mus musculus Translationally-controlled tumor protein Proteins 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 108091008758 NR0A5 Proteins 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 238000009004 PCR Kit Methods 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 101710089118 Probable cytosol aminopeptidase Proteins 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
- 101000720976 Schizosaccharomyces pombe (strain 972 / ATCC 24843) ATP-dependent helicase dcr1 Proteins 0.000 description 1
- 101000781972 Schizosaccharomyces pombe (strain 972 / ATCC 24843) Protein wos2 Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 101001009610 Toxoplasma gondii Dense granule protein 5 Proteins 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 108091029511 Transcript of unknown function Proteins 0.000 description 1
- 102100040250 Transcription elongation factor A protein-like 1 Human genes 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 208000026594 alcoholic fatty liver disease Diseases 0.000 description 1
- 208000002353 alcoholic hepatitis Diseases 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- 101150087698 alpha gene Proteins 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical group OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000012993 chemical processing Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940052810 complex b Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 208000024558 digestive system cancer Diseases 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 230000023011 digestive tract development Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 210000001705 ectoderm cell Anatomy 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000010102 embolization Effects 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 210000004039 endoderm cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000002594 fluoroscopy Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000010231 gastrointestinal system cancer Diseases 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 238000012165 high-throughput sequencing Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000010468 interferon response Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000003780 keratinization Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 230000029795 kidney development Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000007443 liposuction Methods 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000031142 liver development Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 210000001704 mesoblast Anatomy 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- SENLDUJVTGGYIH-UHFFFAOYSA-N n-(2-aminoethyl)-3-[[3-(2-aminoethylamino)-3-oxopropyl]-[2-[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]ethyl]amino]propanamide Chemical compound NCCNC(=O)CCN(CCC(=O)NCCN)CCN(CCC(=O)NCCN)CCC(=O)NCCN SENLDUJVTGGYIH-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 208000009928 nephrosis Diseases 0.000 description 1
- 231100001027 nephrosis Toxicity 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 108091008104 nucleic acid aptamers Proteins 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 238000012634 optical imaging Methods 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 150000003141 primary amines Chemical group 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 238000012764 semi-quantitative analysis Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 102000023888 sequence-specific DNA binding proteins Human genes 0.000 description 1
- 108091008420 sequence-specific DNA binding proteins Proteins 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 102000014898 transaminase activity proteins Human genes 0.000 description 1
- 230000037426 transcriptional repression Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000000264 venule Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000001086 yeast two-hybrid system Methods 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 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
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- 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
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- 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
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
- C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
- Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
a)CD34+細胞に関する組織又は血液試料の富化と、
b)試料を固体支持体と接触させて、該固体支持体に接着する細胞を採取することとによって、得ることと、に更に特徴がある。好適な組織又は血液試料としては、骨髄、末梢血液、臍帯血又は組織、胎盤及び脂肪吸引法で得られる試料が挙げられる。
組織又は血液試料(好ましくは、血液又は骨髄試料などの造血組織)を密度勾配分離にかけることと、
低密度細胞をCD34に関する親和性リガンド(好ましくは常磁性ビーズに付着された)に曝すことと、
該CD34リガンドに付着した細胞を回収することと、
CD34+サブ集団を組織培養等級のプラスチックに曝すことと、
プラスチックに接着性のCD34+細胞を回収することと、によって取得可能である。
a)標的RNA転写物及び標的遺伝子のプロモータ領域は、長さが等しく、これらはその長さ全体にわたって重複する(すなわち、これらは相補的である)。
b)標的RNA転写物は、標的遺伝子のプロモータ領域よりも短く、標的遺伝子のプロモータ領域とその長さ全体にわたって重複する(すなわち、これは標的遺伝子のプロモータ領域内の配列にその長さ全体にわたって相補的である)。
c)標的RNA転写物は、標的遺伝子のプロモータ領域よりも長く、標的遺伝子のプロモータ領域はこれによって完全に重複されている(すなわち、標的遺伝子のプロモータ領域は、標的RNA転写物内の配列にその長さ全体にわたって相補的である)。
d)標的RNA転写物と標的遺伝子のプロモータ領域は同一又は異なる長さであり、重複の領域は、標的RNA転写物の長さ及び標的遺伝子のプロモータ領域の長さの双方よりも短い。
7:520(17頁)で記載され参照されるものを含む。
antisense and RNAi experiments with boosted genetic programming」、Pal Saetrom著、(2004年)、Bioinformatics 20(17):3055−3063に開示され、その内容は参照により本明細書に組み込まれる。あるいは又はこれに加えて、短鎖RNA分子は、高度に有効なsiRNAsに関連する特異的配列特徴を有する。Reynoldsにより記載されたアルゴリズム[Reynoldsら著、(2004年)、Nature biotechnology 22(3):326−330](これは参照により本明細書に組み込まれる)は、短鎖RNAsがこのタイプの十分な特徴を有するかどうかの判定を可能にする。当業者であれば、彼の特定の目的にために、閾値を定義しかつ改良することができるであろう。
Research 第31巻、第13番、3429−3431頁)によって計算され得る。好ましくは、RNAfoldによって計算されるような二本鎖熱力学的末端安定性における差の絶対値は、0kcal/モルを超え、より好ましくは1kcal/モルを超え、より好ましくは3kcal/モルを超える。
過剰増殖性障害及び/又は低アルブミン血症を特徴とする障害の治療又は予防における使用のためのアルブミン産生をアップレギュレートする短鎖活性化RNA。
[本発明1002]
前記過剰増殖性障害が、肝臓癌である、本発明1001の使用のための本発明1001の短鎖活性化RNA。
[本発明1003]
前記低アルブミン血症を特徴とする障害が、肝硬変、肝炎又は浮腫である、本発明1001の使用のための本発明1001の短鎖活性化RNA。
[本発明1004]
前記短鎖活性化RNAが、アルブミン、CEBPA及びHNF4aからなる群から選択される標的遺伝子を活性化することによりアルブミン産生をアップレギュレートする、本発明1001〜1003のいずれかの使用のための本発明1001〜1003のいずれかの短鎖活性化RNA。
[本発明1005]
前記短鎖活性化RNAが、標的RNA転写物を特異的にダウンレギュレートし、
(i)前記標的RNA転写物が、前記標的遺伝子の前記転写開始部位の500ヌクレオチド上流と500ヌクレオチド下流との間の前記標的遺伝子の前記コード鎖上に位置する配列に相補的であることと、
(ii)前記短鎖活性化RNAが、前記標的転写物の領域に少なくとも95%の相補性を有する少なくとも18ヌクレオチドの配列を含むことと、を特徴とする、本発明1004の使用のための本発明1004の短鎖活性化RNA。
[本発明1006]
前記短鎖活性化RNA分子が、最大30ヌクレオチド長の一本鎖又は二本鎖RNA分子である、本発明1001〜1005のいずれかの使用のための本発明1001〜1005のいずれかの短鎖活性化RNA。
[本発明1007]
前記短鎖活性化RNAが、配列番号14、16、8、6、10、12、18、20、22、24、26、28、30、32、34及び36から選択される配列を有する第1鎖を含む、本発明1001〜1006のいずれかの使用のための本発明1001〜1006のいずれかの短鎖活性化RNA。
[本発明1008]
前記短鎖活性化RNAが、配列番号13の配列を有する第2鎖と塩基対を形成する配列番号14の配列を有する第1鎖を含む、本発明1007の使用のための本発明1007の短鎖活性化RNA。
[本発明1009]
アルブミン産生をアップレギュレートすることで、細胞増殖を阻害することが可能な短鎖活性化RNA。
[本発明1010]
前記短鎖活性化RNAが、配列番号14、16、8、6、10、12、18、20、22、24、26、28、30、32、34及び36から選択される配列を有する第1鎖を含む、本発明1009の短鎖活性化RNA。
[本発明1011]
前記短鎖活性化RNAが、配列番号13、15、7、5、9、11、17、19、21、23、25、27、29、31、33及び35から選択される配列を有する第2鎖を含む、本発明1010の短鎖活性化RNA。
[本発明1012]
前記短鎖活性化RNAが、配列番号14の配列を有する第1鎖と配列番号13を有する第2鎖とを有する、本発明1009の短鎖活性化RNA。
[本発明1013]
細胞中のアルブミン発現をアップレギュレートする方法であって、前記方法が、前記細胞を本発明1009〜1012のいずれかの短鎖活性化RNAでトランスフェクトすることを含む、方法。
[本発明1014]
前記細胞が、幹細胞である、本発明1013の方法。
[本発明1015]
本発明1009〜1012のいずれかの短鎖活性化RNAを含む、又は本発明1013又は1014の方法により得ることが可能であるエクスビボ又はインビトロ細胞であって、短鎖活性化RNAを有しない同等の細胞よりも多くのアルブミンを発現する、細胞。
[本発明1016]
過剰増殖性障害及び/又は低アルブミン血症を特徴とする障害を治療する又は予防する方法であって、前記方法が、これを必要とする被験者に、アルブミン産生をアップレギュレートする短鎖活性化RNAを投与することを含む、方法。
[本発明1017]
方法であって、
ある型の細胞の過剰増殖を特徴とする状態を有する患者を診断することと、
前記ある型の細胞によるアルブミンの産生をアップレギュレートする短鎖活性化RNAを設計することと、を含む方法であり、前記アルブミンの前記アップレギュレートされた産生が前記ある型の細胞の増殖能に悪影響を与える、方法。
[本発明1018]
前記短鎖活性化RNAを製造することと、好ましくは前記設計された短鎖活性化RNAを前記患者に投与することとを更に含む、本発明1017の方法。
[本発明1019]
前記診断することが、肝臓癌を診断する、本発明1017又は1018の方法。
[本発明1020]
前記設計することが、アルブミンに関するコード領域を有する遺伝子の転写開始部位を提供することに応答して、コンピュータ読み取り可能な記憶媒体に記憶された1つ以上の命令を実行することを含む、本発明1017〜1019のいずれかの方法。
[本発明1021]
コンピュータ実行可能な命令を含む1つ以上のコンピュータ読み取り可能媒体読み取り可能媒体であって、前記コンピュータ実行可能な命令が、計算システムに、
アルブミンに関するコード領域を有する遺伝子のための転写開始部位を受信することと、
前記転写開始部位の周辺の囲まれた領域を選択することと、
アルブミンの産生をアップレグレートするための短鎖活性化RNA候補物質に関してユニットのストリングを特性化することと、
1つ以上の特性化されたユニットのストリングを、肝臓癌を治療するためのヒト被験者への投与用の短鎖活性化RNAの製造のための好ましい候補物質として出力することと、を指示する、1つ以上のコンピュータ読み取り可能媒体。
本明細書に記載される様々な方法、装置、アセンブリ、システム、配置等、並びにその等価物のより完全な理解は、添付の図面で示される例と併せて使用する場合、以下の詳細な説明を参照することによりなされ得る。
Step RT−PCR(Qiagen ドイツ)を使用して(例えば、製造業者の使用説明書に従って)、逆転写した。アルブミンに関する発現及び負荷対照、ハウスキーピング遺伝子アクチンに関する発現は、これらの対応のプライマー対:アルブミン−F:TCC AGC ACT GCC TGC GGT GA;R:TCC GTC ACG CAC TGG GAG GA;以下の37サイクル:95℃―45秒;55℃−45秒;61℃−45秒、アクチン−F:GAG AAA ATC TGG CAC CAC ACC:R:ATA CCC CTC GTA GAT GGG CAC、以下の37サイクル95℃−5分;60℃−30秒;70℃−45秒;37サイクルで72℃−10分。産生物を、UVP VisonWorks LS(バージョン6.2)を使用して半定量的に3回にわたって分析した。
1.短鎖活性化RNAであって、
哺乳類細胞のポリペプチドのアップレギュレーションを引き起こすためのユニットの配列を含み、哺乳類細胞によるポリペプチドの産生が、哺乳類細胞の増殖能に悪影響を与える、短鎖活性化RNA。
Akira,S.、Isshiki,H.、Sugita,T.、Tanabe,O.、Kinoshita,S.、Nishio,Y.、Nakajima,T.、Hirano,T.及びKishimoto,T.著、(1990年)、「A nuclear factor for IL−6 expression(NF−IL6)is a member of a C/EBP family」、EMBO J 9、1897−1906.
Akira,S.、Nishio,Y.、Inoue,M.、Wang,X.J.、Wei,S.、Matsusaka,T.、Yoshida,K.、Sudo,T.、Naruto,M.及びKishimoto,T.著、(1994年)、「Molecular cloning of APRF,a novel IFN−stimulated
gene factor 3 p91−related transcription
factor involved in the gp130−mediated signaling pathway」、Cell 77、63−71.
Barone,M.V.、Crozat,A.、Tabaee, A.、Philipson,L.、及びRon,D.著、(1994年)、「CHOP(GADD153) and its oncogenic variant,TLS−CHOP,have opposing effects on the induction of G1/S arrest」、Genes Dev 8、453−464.
Buck,M.、Turler,H.、及びChojkier,M.著、(1994年)「LAP(NF−IL−6),a tissue−specific transcriptional activator,is an inhibitor of hepatoma cell proliferation」、EMBO J 13、851−860.
Cao,Z.、Umek,R.M、及びMcKnight,S.L.著、(1991年)、「Regulated expression of three C/EBP isoforms during adipose conversion of 3T3−L1 cells.Genes Dev 5、1538−1552.
Chang,C.J.、Chen,T.T.、Lei,H.Y.、Chen,D.S.、及びLee,S.C.著、(1990年)「Molecular cloning of a transcription factor,AGP/EBP,that belongs to members of the C/EBP family」、Mol Cell Biol 10、6642−6653.
Courtois,G.、Baumhueter,S.、及びCrabtree,G.R.著、(1988年)「Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte−specific promoters」、Proc Natl Acad Sci USA 85、7937−7941.
Descombes,P.、Chojkier,M.、Lichtsteiner,S.、Falvey,E.、及びSchibler,U.著、(1990年)、「LAP,
a novel member of the C/EBP gene family,encodes a liver−enriched transcriptional activator protein」、Genes Dev 4、1541−1551.
Gordon,M.Y.、Levicar,N.、Pai,M.、Bachellier,P.、Dimarakis,I.、Al−Allaf,F.、M’Hamdi,H.、Thalji,T.、Welsh,J.P.、Marley,S.B.ら著(2006年)、「Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony−stimulating factor」、Stem Cells 24、1822−1830.
Hayhurst,G.P.、Lee,Y.H.、Lambert,G.、Ward,J.M.、及びGonzalez,F.J.著、(2001年)、「Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1)is essential for maintenance of hepatic gene expression and lipid homeostasis」、Mol Cell Biol 21、1393−1403.
Itoh,T.、Shiro,T.、Seki,T.、Nakagawa,T.、Wakabayashi,M.、Inoue,K.、及びOkamura,A.(2000年)、「Relationship between p53 overexpression and the proliferative activity in hepatocellular carcinoma」、Int J Mol Med 6、137−142.
Johnson,P.F.著、(2005年)、「Molecular stop signs: regulation of cell−cycle arrest by
C/EBP transcription factors」、J Cell Sci
118、2545−2555.
Kubicka,S.、Kuhnel,F.、Zender,L.、Rudolph,K.L.、Plumpe,J.、Manns,M.、及びTrautwein,C.著、(1999年)、「p53 represses CAAT enhancer−binding protein(C/EBP)−dependent transcription of the albumin gene.A molecular mechanism involved in viral liver infection with implications for hepatocarcinogenesis」、J Biol Chem 274、32137−32144.
Landschulz,W.H.、Johnson,P.F.、及びMcKnight,S.L.著、(1988年)、「The leucine zipper:a hypothetical structure common to a new class of DNA binding proteins」、Science 240、1759−1764.
Lee,Y.H.、Sauer,B.、Johnson,P.F.、及びGonzalez,F.J.著、(1997年)、「Disruption of the c/ebp alpha gene in adult mouse liver」、Mol Cell Biol 17、6014−6022.
Lichtsteiner,S.、及びSchibler,U.著、(1989年)、「A glycosylated liver−specific transcription factor stimulates transcription of the albumin gene」、Cell 57、1179−1187.
Maeda,Y.、Seidel,S.D.、Wei,G.、Liu,X.、及びSladek,F.M.著、(2002年)、「Repression of hepatocyte nuclear factor 4alpha tumor suppressor p53:involvement of the ligand−binding domain and histone deacetylase activity」Mol Endocrinol 16、402−410.
Maire,P.、Wuarin,J.、及びSchibler,U.著、(1989年)、「The role of cis−acting promoter elements in tissue−specific albumin gene expression」、Science 244、343−346.
Mueller,C.R.、Maire,P.、及びSchibler,U.著、(1990年)、「DBP, a liver−enriched transcriptional activator,is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally」、Cell 61、279−291.
Nagao,T.、Kondo, F., Sato, T., Nagato, Y., and Kondo,Y.著、(1995年)、「Immunohistochemical detection of aberrant p53 expression in hepatocellular carcinoma:correlation with cell proliferative activity indices,including mitotic index and MIB−1 immunostaining」、Hum Pathol 26、326−333.
Ng,I.O.、Lai,E.C.、Chan,A.S.、及びSo,M.K.著、(1995年)、「Overexpression of p53 in hepatocellular carcinomas:a clinicopathological
and prognostic correlation」、J Gastroenterol Hepatol 10、250−255.
Panduro,A.、Shalaby,F.、及びShafritz,D.A.著、(1987年)、「Changing patterns of transcriptional and post−transcriptional control of liver−specific gene expression during rat development」、Genes Dev 1、1172−1182.
Pietrangelo,A.、Panduro,A.、Chowdhury,J.R.及びShafritz,D.A.著、(1992年)、「Albumin gene expression is down−regulated by albumin or macromolecule infusion in the rat」、J Clin Invest 89、1755−1760.
Pietrangelo,A.、及びShafritz,D.A.著、(1994年)、「Homeostatic regulation of hepatocyte nuclear transcription factor 1 expression
in cultured hepatoma cells」、Proc Natl Acad Sci USA 91、182−186.
Poli,V.、Mancini,F.P.、及びCortese,R.著、(1990年)、「IL−6DBP,a nuclear protein involved in interleukin−6 signal transduction,defines a new family of leucine zipper proteins related to C/EBP」、Cell 63、643−653.
Prives,C.著、(1998年)、「Signaling to p53: breaking the MDM2−p53 circuit」、Cell 95、5−8.
Tilghman,S.M.、及びBelayew,A.著、(1982年)、「Transcriptional control of the murine albumin/alpha−fetoprotein locus during development」、Proc Natl Acad Sci USA 79、5254−5257.
Trautwein,C.、Boker,K.、及びManns,M.P.著、(1994年)、「Hepatocyte and immune system:acute
phase reaction as a contribution to early defence mechanisms」Gut 35、1163−1166.
Wang,N.D.、Finegold,M.J.、Bradley,A.、Ou,C.N.、Abdelsayed,S.V.、Wilde,M.D.、Taylor,L.R.、Wilson,D.R.、及びDarlington,G.J.著、(1995年)、「Impaired energy homeostasis in C/EBP alpha knockout mice」、Science 269、1108−1112.
Williams,S.C.、Cantwell,C.A.、及びJohnson,P.F.著、(1991年)、「A family of C/EBP−related proteins capable of forming covalently linked leucine zipper dimers in vitro」、Genes Dev 5、1553−1567.
Zhong,Z.、Wen,Z.、及びDarnell,J.E.,Jr.著、(1994年)、「Stat3:a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin−6」、Science 264、95−98.
アルブミン産生に関与する遺伝子の遺伝子配列を、短鎖活性化RNA分子をその特異的な活性化に関して設計するために選択した。特に好適なものはアルブミン遺伝子、CEBPA遺伝子及び/又はHNF4アルファ遺伝子である。
材料及び方法
実施例1に記載のように設計された25nMのアニールしたアルブミンsaRNAを、製造業者の使用説明書に従って、ナノフェクタミン(PAA、英国)を使用して細胞の単層上にトランスフェクトした。このプロセスは、3回繰り返した。この試験に使用されたsaRNAの配列は、表1に示すような、ヒトアルブミンPR1(配列番号5及び配列番号6)、ヒトアルブミンPR2(配列番号7及び配列番号8)、ヒトアルブミンPR3(配列番号9及び配列番号10)及びヒトアルブミンPR4(配列番号11及び配列番号12)であった。無作為の、スクランブルされたRNA分子を対照として使用した。
ELISA、Assay Pro USA)用に、製造業者の使用説明書に従って、培養基を回収した。
結果
HepG2細胞及びラット肝臓上皮細胞を、実施例2で記載される通りにアルブミンsaRNAでトランスフェクトした(すなわち、本実施例では、実施例2と同一のsaRNAを使用した)。ラット肝臓上皮細胞及びHepG2細胞内のそれぞれの細胞増殖を、WSR−1増殖アッセイを使用して測定した。簡単に言うと、細胞増殖試薬のテトラゾリウム塩、4−[3−(4−ヨードフェニル)2−(4ニトロフェニル)2H−5−テトラゾリオ]1,3−ベンゼンジスルホネート(Roche Applied Science、英国)を加えた(例えば、製造業者の使用説明書に従って)。次いで比色アッセイを30分間インキュベートし、生存細胞中のミトコンドリアスクシネート−テトラゾリウムレダクターゼによるテトラゾリウム塩WST−1のホルマザン染料への切断を可能にした。増殖する代謝的に活性な細胞の数に直接関連するホルマザン染料の量を、マルチウェルプレートリーダーにおいてAmax450nmで測定した。
以下のCEBPAを標的としたsaRNA二本鎖(センス/アンチセンス)を、この試験で使用した。
AW1センス鎖:CGGUCAUUGUCACUGGUCA(配列番号13)
AW1アンチセンス鎖:UGACCAGUGACAAUGACCG(配列番号14)
AW2センス鎖:AGCUGAAAGGAUUCAUCCU(配列番号15)
AW2アンチセンス鎖:AGGAUGAAUCCUUUCAGCU(配列番号16)
10匹の雄C57BI6/J、8週齢マウスを実験に使用した(対照群N=5)。施設及び地域規制機関からの承認を得、全ての手順は常任の国家条例に従った。
CEBPA saRNA構築物のアルブミンを増加させる能力を、罹患動物、すなわち肝硬変を有するラットで評価した。
20匹のラットを、四塩化炭素(CCl4)で処置して、肝硬変を惹起させた。ラットは、40mL/Lの濃度において、0.2mL/100g体重のCCl4で、週2回4週間にわたって処置した。
実施例6又は7で記載された実験を、肝臓癌を有するよう化学的に惹起させたマウスで繰り返す。肝臓癌は、DEN、遺伝毒性のある発癌物質を使用して惹起させる。DENは、典型的には、単回腹腔内注射(15μg/g体重)により、12日齢と15日齢の間のマウスに投与する。このプロトコルを使用することにより、平均で、DENの腹腔内注射後44週に、B6C3F1雄マウスの100%がHCCsを発生する。次いで、表1に示すsaRNAsを投与し、アルブミン発現を、実施例6に記載されるようにアッセイする。
ヒト肝臓腫瘍細胞をインビトロで培養し、洗浄し、ヌードマウス(4〜6週齢)の下部脇腹部位に皮下注射する(3.0×106細胞)。表1に示すsaRNAを使用する療法を、腫瘍が〜50−60mm3の平均体積に到達した1〜3週間後に開始する。腫瘍直径をディジタル式ノギスで測定し、mm3での腫瘍体積を、式:体積=(幅)2×長さ/2により計算する。
Claims (21)
- 過剰増殖性障害及び/又は低アルブミン血症を特徴とする障害の治療又は予防における使用のためのアルブミン産生をアップレギュレートする短鎖活性化RNA。
- 前記過剰増殖性障害が、肝臓癌である、請求項1に記載の使用のための請求項1に記載の短鎖活性化RNA。
- 前記低アルブミン血症を特徴とする障害が、肝硬変、肝炎又は浮腫である、請求項1に記載の使用のための請求項1に記載の短鎖活性化RNA。
- 前記短鎖活性化RNAが、アルブミン、CEBPA及びHNF4aからなる群から選択される標的遺伝子を活性化することによりアルブミン産生をアップレギュレートする、請求項1〜3のいずれか一項に記載の使用のための請求項1〜3のいずれか一項に記載の短鎖活性化RNA。
- 前記短鎖活性化RNAが、標的RNA転写物を特異的にダウンレギュレートし、(i)前記標的RNA転写物が、前記標的遺伝子の前記転写開始部位の500ヌクレオチド上流と500ヌクレオチド下流との間の前記標的遺伝子の前記コード鎖上に位置する配列に相補的であることと、
(ii)前記短鎖活性化RNAが、前記標的転写物の領域に少なくとも95%の相補性を有する少なくとも18ヌクレオチドの配列を含むことと、を特徴とする、請求項4に記載の使用のための請求項4に記載の短鎖活性化RNA。 - 前記短鎖活性化RNA分子が、最大30ヌクレオチド長の一本鎖又は二本鎖RNA分子である、請求項1〜5のいずれか一項に記載の使用のための請求項1〜5のいずれか一項に記載の短鎖活性化RNA。
- 前記短鎖活性化RNAが、配列番号14、16、8、6、10、12、18、20、22、24、26、28、30、32、34及び36から選択される配列を有する第1鎖を含む、請求項1〜6のいずれか一項に記載の使用のための請求項1〜6のいずれか一項に記載の短鎖活性化RNA。
- 前記短鎖活性化RNAが、配列番号13の配列を有する第2鎖と塩基対を形成する配列番号14の配列を有する第1鎖を含む、請求項7に記載の使用のための請求項7に記載の短鎖活性化RNA。
- アルブミン産生をアップレギュレートすることで、細胞増殖を阻害することが可能な短鎖活性化RNA。
- 前記短鎖活性化RNAが、配列番号14、16、8、6、10、12、18、20、22、24、26、28、30、32、34及び36から選択される配列を有する第1鎖を含む、請求項9に記載の短鎖活性化RNA。
- 前記短鎖活性化RNAが、配列番号13、15、7、5、9、11、17、19、21、23、25、27、29、31、33及び35から選択される配列を有する第2鎖を含む、請求項10に記載の短鎖活性化RNA。
- 前記短鎖活性化RNAが、配列番号14の配列を有する第1鎖と配列番号13を有する第2鎖とを有する、請求項9に記載の短鎖活性化RNA。
- 細胞中のアルブミン発現をアップレギュレートする方法であって、前記方法が、前記細胞を請求項9〜12のいずれか一項に記載の短鎖活性化RNAでトランスフェクトすることを含む、方法。
- 前記細胞が、幹細胞である、請求項13に記載の方法。
- 請求項9〜12のいずれか一項に記載の短鎖活性化RNAを含む、又は請求項13又は14に記載の方法により得ることが可能であるエクスビボ又はインビトロ細胞であって、短鎖活性化RNAを有しない同等の細胞よりも多くのアルブミンを発現する、細胞。
- 過剰増殖性障害及び/又は低アルブミン血症を特徴とする障害を治療する又は予防する方法であって、前記方法が、これを必要とする被験者に、アルブミン産生をアップレギュレートする短鎖活性化RNAを投与することを含む、方法。
- 方法であって、
ある型の細胞の過剰増殖を特徴とする状態を有する患者を診断することと、
前記ある型の細胞によるアルブミンの産生をアップレギュレートする短鎖活性化RNAを設計することと、を含む方法であり、前記アルブミンの前記アップレギュレートされた産生が前記ある型の細胞の増殖能に悪影響を与える、方法。 - 前記短鎖活性化RNAを製造することと、好ましくは前記設計された短鎖活性化RNAを前記患者に投与することとを更に含む、請求項17に記載の方法。
- 前記診断することが、肝臓癌を診断する、請求項17又は18に記載の方法。
- 前記設計することが、アルブミンに関するコード領域を有する遺伝子の転写開始部位を提供することに応答して、コンピュータ読み取り可能な記憶媒体に記憶された1つ以上の命令を実行することを含む、請求項17〜19のいずれか一項に記載の方法。
- コンピュータ実行可能な命令を含む1つ以上のコンピュータ読み取り可能媒体読み取り可能媒体であって、前記コンピュータ実行可能な命令が、計算システムに、
アルブミンに関するコード領域を有する遺伝子のための転写開始部位を受信することと、
前記転写開始部位の周辺の囲まれた領域を選択することと、
アルブミンの産生をアップレグレートするための短鎖活性化RNA候補物質に関してユニットのストリングを特性化することと、
1つ以上の特性化されたユニットのストリングを、肝臓癌を治療するためのヒト被験者への投与用の短鎖活性化RNAの製造のための好ましい候補物質として出力することと、を指示する、1つ以上のコンピュータ読み取り可能媒体。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022152260A JP2022173343A (ja) | 2011-06-21 | 2022-09-26 | アルブミン産生及び細胞増殖 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161499637P | 2011-06-21 | 2011-06-21 | |
US61/499,637 | 2011-06-21 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019024365A Division JP6742459B2 (ja) | 2011-06-21 | 2019-02-14 | アルブミン産生及び細胞増殖 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022152260A Division JP2022173343A (ja) | 2011-06-21 | 2022-09-26 | アルブミン産生及び細胞増殖 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021003106A true JP2021003106A (ja) | 2021-01-14 |
JP7177520B2 JP7177520B2 (ja) | 2022-11-24 |
Family
ID=46395639
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014516440A Active JP5993002B2 (ja) | 2011-06-21 | 2012-06-20 | アルブミン産生及び細胞増殖 |
JP2016160357A Active JP6483645B2 (ja) | 2011-06-21 | 2016-08-18 | アルブミン産生及び細胞増殖 |
JP2019024365A Active JP6742459B2 (ja) | 2011-06-21 | 2019-02-14 | アルブミン産生及び細胞増殖 |
JP2020126934A Active JP7177520B2 (ja) | 2011-06-21 | 2020-07-28 | アルブミン産生及び細胞増殖 |
JP2022152260A Pending JP2022173343A (ja) | 2011-06-21 | 2022-09-26 | アルブミン産生及び細胞増殖 |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014516440A Active JP5993002B2 (ja) | 2011-06-21 | 2012-06-20 | アルブミン産生及び細胞増殖 |
JP2016160357A Active JP6483645B2 (ja) | 2011-06-21 | 2016-08-18 | アルブミン産生及び細胞増殖 |
JP2019024365A Active JP6742459B2 (ja) | 2011-06-21 | 2019-02-14 | アルブミン産生及び細胞増殖 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022152260A Pending JP2022173343A (ja) | 2011-06-21 | 2022-09-26 | アルブミン産生及び細胞増殖 |
Country Status (6)
Country | Link |
---|---|
US (6) | US9284553B2 (ja) |
EP (3) | EP2723862B1 (ja) |
JP (5) | JP5993002B2 (ja) |
KR (2) | KR102039315B1 (ja) |
CN (1) | CN103842508B (ja) |
WO (1) | WO2012175958A1 (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6621409B2 (ja) * | 2013-11-22 | 2019-12-18 | ミナ セラピューティクス リミテッド | C/EBPα小分子活性化RNA組成物 |
WO2015162422A1 (en) * | 2014-04-22 | 2015-10-29 | Mina Therapeutics Limited | Sarna compositions and methods of use |
WO2016145608A1 (zh) * | 2015-03-17 | 2016-09-22 | 中国医学科学院北京协和医院 | 一种小激活rna及其制备方法和应用 |
CN106032532A (zh) * | 2015-03-17 | 2016-10-19 | 中国医学科学院北京协和医院 | 一种小激活rna及其制备方法和应用 |
WO2016170349A1 (en) | 2015-04-22 | 2016-10-27 | Mina Therapeutics Limited | C/ebp alpha sarna compositions and methods of use |
EP4233880A3 (en) | 2017-09-08 | 2023-09-20 | MiNA Therapeutics Limited | Hnf4a sarna compositions and methods of use |
US20200208152A1 (en) | 2017-09-08 | 2020-07-02 | Mina Therapeutics Limited | Stabilized sarna compositions and methods of use |
US20210254069A1 (en) | 2018-06-15 | 2021-08-19 | Mina Therapeutics Limited | Combination therapies comprising c/ebp alpha sarna |
WO2021032777A1 (en) | 2019-08-19 | 2021-02-25 | Mina Therapeutics Limited | Oligonucleotide conjugate compositions and methods of use |
WO2021052470A1 (zh) * | 2019-09-20 | 2021-03-25 | 中美瑞康核酸技术(南通)研究院有限公司 | 用于治疗血小板减少症的核酸分子及其应用 |
CN111671913B (zh) * | 2020-07-30 | 2022-02-08 | 四川大学 | 一种量子点-小核酸偶联物及其用途 |
WO2022229644A1 (en) | 2021-04-28 | 2022-11-03 | Mina Therapeutics Limited | Combination therapies comprising c/ebp alpha sarna |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003113096A (ja) * | 2001-10-04 | 2003-04-18 | Pola Chem Ind Inc | アルブミン合成促進剤 |
JP2008538896A (ja) * | 2005-04-15 | 2008-11-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 小分子活性化rna分子及び使用方法 |
JP2010006764A (ja) * | 2008-06-27 | 2010-01-14 | Ajinomoto Co Inc | タンパク同化促進剤 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6306655B1 (en) * | 2000-06-13 | 2001-10-23 | Isis Pharmaceuticals, Inc. | Antisense inhibition of C/EBP alpha expression |
US8090542B2 (en) * | 2002-11-14 | 2012-01-03 | Dharmacon Inc. | Functional and hyperfunctional siRNA |
GB0329449D0 (en) | 2003-12-19 | 2004-01-28 | Omnicyte Ltd | Stem cells |
CN101524529B (zh) * | 2008-03-04 | 2011-09-28 | 中国人民解放军第二军医大学 | HNF4α诱导分化治疗人体恶性实体瘤 |
CN101491527B (zh) * | 2009-03-03 | 2011-05-25 | 山东大学 | 四氢嘧啶在制备治疗肝炎或肝硬化药物中的应用 |
US8962583B2 (en) * | 2009-06-25 | 2015-02-24 | The Brigham And Women's Hospital, Inc. | Treatment of inflammatory diseases using miR-124 |
CN102822342B (zh) * | 2010-01-06 | 2017-05-10 | 库尔纳公司 | 通过抑制胰腺发育基因的天然反义转录物而治疗胰腺发育基因相关疾病 |
-
2012
- 2012-06-20 WO PCT/GB2012/051422 patent/WO2012175958A1/en active Application Filing
- 2012-06-20 EP EP12730246.1A patent/EP2723862B1/en active Active
- 2012-06-20 JP JP2014516440A patent/JP5993002B2/ja active Active
- 2012-06-20 EP EP22163516.2A patent/EP4060043A1/en active Pending
- 2012-06-20 CN CN201280030756.XA patent/CN103842508B/zh active Active
- 2012-06-20 EP EP18189270.4A patent/EP3456828B1/en active Active
- 2012-06-20 KR KR1020147001446A patent/KR102039315B1/ko active IP Right Grant
- 2012-06-20 KR KR1020197031287A patent/KR102195514B1/ko active IP Right Grant
- 2012-06-20 US US14/128,147 patent/US9284553B2/en active Active
-
2016
- 2016-02-02 US US15/013,866 patent/US9745579B2/en active Active
- 2016-08-18 JP JP2016160357A patent/JP6483645B2/ja active Active
-
2017
- 2017-07-21 US US15/656,000 patent/US9944930B2/en active Active
-
2018
- 2018-03-08 US US15/915,275 patent/US10704044B2/en active Active
-
2019
- 2019-02-14 JP JP2019024365A patent/JP6742459B2/ja active Active
-
2020
- 2020-05-22 US US16/881,134 patent/US20200283771A1/en not_active Abandoned
- 2020-07-28 JP JP2020126934A patent/JP7177520B2/ja active Active
-
2022
- 2022-09-26 JP JP2022152260A patent/JP2022173343A/ja active Pending
-
2023
- 2023-05-12 US US18/316,556 patent/US20240002854A1/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003113096A (ja) * | 2001-10-04 | 2003-04-18 | Pola Chem Ind Inc | アルブミン合成促進剤 |
JP2008538896A (ja) * | 2005-04-15 | 2008-11-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 小分子活性化rna分子及び使用方法 |
JP2010006764A (ja) * | 2008-06-27 | 2010-01-14 | Ajinomoto Co Inc | タンパク同化促進剤 |
Non-Patent Citations (2)
Title |
---|
PLOS ONE, 2010, VOL.5, NO.1, E8848, JPN6020002415, ISSN: 0004790915 * |
PROC NATL ACAD SCI USA, 2006, VOL.103, NO.46, P.17337-17342, JPN6020002413, ISSN: 0004790914 * |
Also Published As
Publication number | Publication date |
---|---|
JP5993002B2 (ja) | 2016-09-14 |
EP4060043A1 (en) | 2022-09-21 |
JP2022173343A (ja) | 2022-11-18 |
US9284553B2 (en) | 2016-03-15 |
KR102195514B1 (ko) | 2020-12-29 |
US10704044B2 (en) | 2020-07-07 |
JP2014519838A (ja) | 2014-08-21 |
US20180201932A1 (en) | 2018-07-19 |
CN103842508B (zh) | 2016-02-24 |
EP3456828B1 (en) | 2022-04-27 |
US9745579B2 (en) | 2017-08-29 |
WO2012175958A1 (en) | 2012-12-27 |
JP2019115345A (ja) | 2019-07-18 |
JP7177520B2 (ja) | 2022-11-24 |
JP6742459B2 (ja) | 2020-08-19 |
KR20190125504A (ko) | 2019-11-06 |
US20240002854A1 (en) | 2024-01-04 |
EP3456828A1 (en) | 2019-03-20 |
US20200283771A1 (en) | 2020-09-10 |
JP6483645B2 (ja) | 2019-03-13 |
EP2723862B1 (en) | 2018-09-19 |
CN103842508A (zh) | 2014-06-04 |
US20170321215A1 (en) | 2017-11-09 |
US20160145618A1 (en) | 2016-05-26 |
EP2723862A1 (en) | 2014-04-30 |
KR102039315B1 (ko) | 2019-11-04 |
US20140228424A1 (en) | 2014-08-14 |
KR20140039307A (ko) | 2014-04-01 |
US9944930B2 (en) | 2018-04-17 |
JP2017035083A (ja) | 2017-02-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6742459B2 (ja) | アルブミン産生及び細胞増殖 | |
Tao et al. | LncRNA GAS5 controls cardiac fibroblast activation and fibrosis by targeting miR-21 via PTEN/MMP-2 signaling pathway | |
Wang et al. | CircUbe3a from M2 macrophage-derived small extracellular vesicles mediates myocardial fibrosis after acute myocardial infarction | |
Ma et al. | Long non‐coding RNA LOC 554202 modulates chordoma cell proliferation and invasion by recruiting EZH 2 and regulating miR‐31 expression | |
Song et al. | lncITPF promotes pulmonary fibrosis by targeting hnRNP-L depending on its host gene ITGBL1 | |
EP2454370B1 (en) | Microrna-24 | |
Zhang et al. | IFN-γ enhances the efficacy of mesenchymal stromal cell-derived exosomes via miR-21 in myocardial infarction rats | |
Liu et al. | Long non-coding RNA CCAL promotes hepatocellular carcinoma progression by regulating AP-2α and Wnt/β-catenin pathway | |
Ye et al. | LPS-inducible lncRNA TMC3-AS1 negatively regulates the expression of IL-10 | |
Rafatian et al. | Mybl2 rejuvenates heart explant‐derived cells from aged donors after myocardial infarction | |
Bae et al. | Gatekeeping role of Nf2/Merlin in vascular tip EC induction through suppression of VEGFR2 internalization | |
Naidoo et al. | MicroRNA-1205 regulation of FRYL in prostate cancer | |
Jiang et al. | The G4 resolvase RHAU modulates mRNA translation and stability to sustain postnatal heart function and regeneration | |
Zhou et al. | Valsartan Regulates PI3K/AKT Pathways through lncRNA GASL1 to Improve Isoproterenol‐Induced Heart Failure | |
CN109097358B (zh) | 一种lncRNA在预防或治疗高血压中的应用 | |
Wang et al. | miR‐409‐3p Regulated by GATA2 Promotes Cardiac Fibrosis through Targeting Gpd1 | |
Gao et al. | lncRNA TRPM2‐AS Promotes Colorectal Cancer Progression by Regulating miR‐22‐3p and FSTL1 | |
US20110110896A1 (en) | Modulating levels of RNA-binding proteins for the treatment of breast cancer | |
Huang et al. | Carbon ion irradiation suppresses angiogenic response in human lung adenocarcinoma cells mediated by LINC00167/miR-663a/TGF-β1 axis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200820 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200820 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201007 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20210427 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210804 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210909 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220121 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20220606 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220926 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20220926 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20221004 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20221005 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20221026 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20221104 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7177520 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |