JP2008537752A - がんおよび他の新血管形成疾患を処置するためのＲＮＡｉ治療用の組成物および方法 - Google Patents
がんおよび他の新血管形成疾患を処置するためのＲＮＡｉ治療用の組成物および方法 Download PDFInfo
- Publication number
- JP2008537752A JP2008537752A JP2008506633A JP2008506633A JP2008537752A JP 2008537752 A JP2008537752 A JP 2008537752A JP 2008506633 A JP2008506633 A JP 2008506633A JP 2008506633 A JP2008506633 A JP 2008506633A JP 2008537752 A JP2008537752 A JP 2008537752A
- Authority
- JP
- Japan
- Prior art keywords
- sirna
- composition
- rna
- vegf
- strand
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 115
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 82
- 238000000034 method Methods 0.000 title claims abstract description 72
- 230000009368 gene silencing by RNA Effects 0.000 title claims abstract description 60
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 49
- 201000010099 disease Diseases 0.000 title claims abstract description 47
- 230000001225 therapeutic effect Effects 0.000 title claims description 23
- 108091030071 RNAI Proteins 0.000 title claims 2
- 201000011510 cancer Diseases 0.000 title abstract description 10
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract description 129
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract description 126
- 230000037361 pathway Effects 0.000 claims abstract description 70
- 239000003814 drug Substances 0.000 claims abstract description 64
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 claims abstract description 58
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 54
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 53
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 53
- 238000011282 treatment Methods 0.000 claims abstract description 51
- 230000014509 gene expression Effects 0.000 claims abstract description 50
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 9
- 108090000623 proteins and genes Proteins 0.000 claims description 121
- 210000004027 cell Anatomy 0.000 claims description 90
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 81
- 230000008685 targeting Effects 0.000 claims description 75
- 210000001519 tissue Anatomy 0.000 claims description 62
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 claims description 55
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims description 55
- 102000058223 human VEGFA Human genes 0.000 claims description 53
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 42
- 108020004459 Small interfering RNA Proteins 0.000 claims description 42
- 229940079593 drug Drugs 0.000 claims description 38
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 claims description 36
- 241000282414 Homo sapiens Species 0.000 claims description 35
- 108091034117 Oligonucleotide Proteins 0.000 claims description 35
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 claims description 33
- 125000003729 nucleotide group Chemical group 0.000 claims description 27
- 239000002773 nucleotide Substances 0.000 claims description 26
- 108020003175 receptors Proteins 0.000 claims description 26
- 102000005962 receptors Human genes 0.000 claims description 25
- 102000004169 proteins and genes Human genes 0.000 claims description 23
- 206010029113 Neovascularisation Diseases 0.000 claims description 19
- 239000013598 vector Substances 0.000 claims description 18
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 108091081021 Sense strand Proteins 0.000 claims description 11
- 230000000692 anti-sense effect Effects 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 229920000768 polyamine Polymers 0.000 claims description 8
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 claims description 7
- 108020004414 DNA Proteins 0.000 claims description 6
- 101100372760 Homo sapiens FLT1 gene Proteins 0.000 claims description 5
- 210000004962 mammalian cell Anatomy 0.000 claims description 5
- 102000055590 human KDR Human genes 0.000 claims description 4
- 238000001338 self-assembly Methods 0.000 claims description 4
- 101710098940 Pro-epidermal growth factor Proteins 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000002068 genetic effect Effects 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 102000053602 DNA Human genes 0.000 claims 1
- 230000004663 cell proliferation Effects 0.000 claims 1
- 210000005067 joint tissue Anatomy 0.000 claims 1
- 230000004654 survival pathway Effects 0.000 claims 1
- 239000002105 nanoparticle Substances 0.000 abstract description 76
- 229920000642 polymer Polymers 0.000 abstract description 59
- 230000005764 inhibitory process Effects 0.000 abstract description 57
- 239000005557 antagonist Substances 0.000 abstract description 12
- 230000008238 biochemical pathway Effects 0.000 abstract description 6
- 206010003246 arthritis Diseases 0.000 abstract description 3
- 208000027866 inflammatory disease Diseases 0.000 abstract description 3
- 208000030533 eye disease Diseases 0.000 abstract description 2
- 230000001023 pro-angiogenic effect Effects 0.000 abstract description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 121
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 51
- 241000699670 Mus sp. Species 0.000 description 44
- 239000003446 ligand Substances 0.000 description 40
- 241001465754 Metazoa Species 0.000 description 37
- 238000012384 transportation and delivery Methods 0.000 description 35
- 230000004614 tumor growth Effects 0.000 description 28
- 230000033115 angiogenesis Effects 0.000 description 27
- 238000002474 experimental method Methods 0.000 description 25
- 238000002347 injection Methods 0.000 description 24
- 239000007924 injection Substances 0.000 description 24
- 108020004999 messenger RNA Proteins 0.000 description 24
- 241000699666 Mus <mouse, genus> Species 0.000 description 23
- 230000000694 effects Effects 0.000 description 23
- 230000001404 mediated effect Effects 0.000 description 21
- 210000001525 retina Anatomy 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- 238000000338 in vitro Methods 0.000 description 19
- 238000001727 in vivo Methods 0.000 description 19
- 229920002873 Polyethylenimine Polymers 0.000 description 15
- 230000008901 benefit Effects 0.000 description 15
- 238000003197 gene knockdown Methods 0.000 description 15
- 230000030279 gene silencing Effects 0.000 description 15
- 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 14
- 230000027455 binding Effects 0.000 description 14
- 239000003112 inhibitor Substances 0.000 description 14
- 238000009472 formulation Methods 0.000 description 13
- 230000003389 potentiating effect Effects 0.000 description 13
- 238000011160 research Methods 0.000 description 13
- 238000010171 animal model Methods 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 12
- 206010009944 Colon cancer Diseases 0.000 description 11
- 229940120638 avastin Drugs 0.000 description 11
- 210000004204 blood vessel Anatomy 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 230000001772 anti-angiogenic effect Effects 0.000 description 10
- 230000000259 anti-tumor effect Effects 0.000 description 10
- 230000004071 biological effect Effects 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 208000029742 colonic neoplasm Diseases 0.000 description 10
- 238000001990 intravenous administration Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000008188 pellet Substances 0.000 description 10
- 239000002202 Polyethylene glycol Substances 0.000 description 9
- 238000004520 electroporation Methods 0.000 description 9
- 238000011081 inoculation Methods 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 238000012385 systemic delivery Methods 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- 210000003462 vein Anatomy 0.000 description 9
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 8
- 241000699660 Mus musculus Species 0.000 description 8
- 238000010253 intravenous injection Methods 0.000 description 8
- 238000010172 mouse model Methods 0.000 description 8
- 238000011580 nude mouse model Methods 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000002207 retinal effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000012447 xenograft mouse model Methods 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 210000002889 endothelial cell Anatomy 0.000 description 7
- 238000002513 implantation Methods 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 238000003757 reverse transcription PCR Methods 0.000 description 7
- YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 108060001084 Luciferase Proteins 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 6
- 208000017442 Retinal disease Diseases 0.000 description 6
- 206010038923 Retinopathy Diseases 0.000 description 6
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 229920001577 copolymer Polymers 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000001939 inductive effect Effects 0.000 description 6
- 239000007928 intraperitoneal injection Substances 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 5
- 206010021143 Hypoxia Diseases 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 108091008605 VEGF receptors Proteins 0.000 description 5
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 5
- 230000002491 angiogenic effect Effects 0.000 description 5
- 229920006317 cationic polymer Polymers 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 229920001477 hydrophilic polymer Polymers 0.000 description 5
- 230000007954 hypoxia Effects 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 102000006495 integrins Human genes 0.000 description 5
- 108010044426 integrins Proteins 0.000 description 5
- 230000002601 intratumoral effect Effects 0.000 description 5
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 230000001717 pathogenic effect Effects 0.000 description 5
- 230000000704 physical effect Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 206010061818 Disease progression Diseases 0.000 description 4
- 239000012979 RPMI medium Substances 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 125000002091 cationic group Chemical group 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000005750 disease progression Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000002452 interceptive effect Effects 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 230000003068 static effect Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000007910 systemic administration Methods 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 229950004616 tribromoethanol Drugs 0.000 description 4
- 239000003656 tris buffered saline Substances 0.000 description 4
- 230000003827 upregulation Effects 0.000 description 4
- 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 3
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 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
- 239000007995 HEPES buffer Substances 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- 239000012097 Lipofectamine 2000 Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 101100372766 Mus musculus Kdr gene Proteins 0.000 description 3
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 3
- 229930182556 Polyacetal Natural products 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 206010038389 Renal cancer Diseases 0.000 description 3
- 208000007135 Retinal Neovascularization Diseases 0.000 description 3
- 102000006382 Ribonucleases Human genes 0.000 description 3
- 108010083644 Ribonucleases Proteins 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 3
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 239000002870 angiogenesis inducing agent Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- -1 c-Met Proteins 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000002222 downregulating effect Effects 0.000 description 3
- 230000003828 downregulation Effects 0.000 description 3
- 230000007783 downstream signaling Effects 0.000 description 3
- 230000005684 electric field Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 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 3
- 238000012226 gene silencing method Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 201000010982 kidney cancer Diseases 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 238000007747 plating Methods 0.000 description 3
- 229920006324 polyoxymethylene Polymers 0.000 description 3
- 230000001124 posttranscriptional effect Effects 0.000 description 3
- 230000004952 protein activity Effects 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 229940054269 sodium pyruvate Drugs 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- STGXGJRRAJKJRG-JDJSBBGDSA-N (3r,4r,5r)-5-(hydroxymethyl)-3-methoxyoxolane-2,4-diol Chemical class CO[C@H]1C(O)O[C@H](CO)[C@H]1O STGXGJRRAJKJRG-JDJSBBGDSA-N 0.000 description 2
- 208000031873 Animal Disease Models Diseases 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 102100023804 Coagulation factor VII Human genes 0.000 description 2
- 206010055665 Corneal neovascularisation Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 108010023321 Factor VII Proteins 0.000 description 2
- 108090000331 Firefly luciferases Proteins 0.000 description 2
- 101150048336 Flt1 gene Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 101000808007 Mus musculus Vascular endothelial growth factor A Proteins 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- 241000244206 Nematoda Species 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- 108010076289 Platelet-Derived Growth Factor Receptors Proteins 0.000 description 2
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 2
- 102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 description 2
- 101710148465 Platelet-derived growth factor receptor alpha Proteins 0.000 description 2
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 2
- 208000005107 Premature Birth Diseases 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000004338 Transferrin Human genes 0.000 description 2
- 108090000901 Transferrin Proteins 0.000 description 2
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 239000004037 angiogenesis inhibitor Substances 0.000 description 2
- 230000006481 angiogenic pathway Effects 0.000 description 2
- 238000011558 animal model by disease Methods 0.000 description 2
- 230000003527 anti-angiogenesis Effects 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229960000397 bevacizumab Drugs 0.000 description 2
- 230000008236 biological pathway Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 201000000159 corneal neovascularization Diseases 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 229920000765 poly(2-oxazolines) Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000004853 protein function Effects 0.000 description 2
- 230000009145 protein modification Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 208000004644 retinal vein occlusion Diseases 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229960002101 secretin Drugs 0.000 description 2
- 230000001743 silencing effect Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000003151 transfection method Methods 0.000 description 2
- 239000012581 transferrin Substances 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 238000010200 validation analysis Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 230000008728 vascular permeability Effects 0.000 description 2
- 230000004862 vasculogenesis Effects 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 1
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 1
- 101150037123 APOE gene Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 238000006418 Brown reaction Methods 0.000 description 1
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
- 101100263580 Canis lupus familiaris VEGFA gene Proteins 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 101100216294 Danio rerio apoeb gene Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000031969 Eye Hemorrhage Diseases 0.000 description 1
- 108010054265 Factor VIIa Proteins 0.000 description 1
- 108060003393 Granulin Proteins 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 101001126417 Homo sapiens Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 102000005755 Intercellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108010070716 Intercellular Signaling Peptides and Proteins Proteins 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 206010027452 Metastases to bone Diseases 0.000 description 1
- 101100118551 Mus musculus Egfr gene Proteins 0.000 description 1
- 101100372761 Mus musculus Flt1 gene Proteins 0.000 description 1
- 101001126413 Mus musculus Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
- 101000692457 Mus musculus Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101001134300 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Multidomain regulatory protein Rv1364c Proteins 0.000 description 1
- 101000615835 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Phosphoserine phosphatase SerB2 Proteins 0.000 description 1
- 101001082202 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Triple specificity protein phosphatase PtpB Proteins 0.000 description 1
- 101001134301 Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh) Multidomain regulatory protein MT1410 Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 101150093908 PDGFRB gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 101000781681 Protobothrops flavoviridis Disintegrin triflavin Proteins 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 102000007238 Transferrin Receptors Human genes 0.000 description 1
- 108010033576 Transferrin Receptors Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
- 101150030763 Vegfa gene Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000004308 accommodation Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- NIGUVXFURDGQKZ-UQTBNESHSA-N alpha-Neup5Ac-(2->3)-beta-D-Galp-(1->4)-[alpha-L-Fucp-(1->3)]-beta-D-GlcpNAc Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](O[C@]3(O[C@H]([C@H](NC(C)=O)[C@@H](O)C3)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O)[C@@H](CO)O2)O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O NIGUVXFURDGQKZ-UQTBNESHSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 230000007416 antiviral immune response Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 229940028881 combination metronidazole Drugs 0.000 description 1
- 229960003950 combination of corticosteroids Drugs 0.000 description 1
- 230000007748 combinatorial effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000007771 core particle Substances 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 206010014801 endophthalmitis Diseases 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700021358 erbB-1 Genes Proteins 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000001232 limbus corneae Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 210000001077 lymphatic endothelium Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229940092110 macugen Drugs 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 201000006958 oropharynx cancer Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000009745 pathological pathway Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 229920002959 polymer blend Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 210000004896 polypeptide structure Anatomy 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 230000032361 posttranscriptional gene silencing Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000011158 quantitative evaluation Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000004263 retinal angiogenesis Effects 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
- 229960004291 sucralfate Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 150000003668 tyrosines Chemical class 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- 230000006496 vascular abnormality Effects 0.000 description 1
- 230000006711 vascular endothelial growth factor production Effects 0.000 description 1
- 210000000264 venule Anatomy 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- 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
- 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
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C12N15/1136—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 against growth factors, growth regulators, cytokines, lymphokines or hormones
-
- 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
- C12N15/1138—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 against receptors or cell surface proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- 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
-
- 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
- C12N2320/31—Combination therapy
-
- 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
- C12N2320/32—Special delivery means, e.g. tissue-specific
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Rheumatology (AREA)
- Optics & Photonics (AREA)
- Endocrinology (AREA)
- Nanotechnology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Communicable Diseases (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67071705P | 2005-04-12 | 2005-04-12 | |
| PCT/US2006/013645 WO2006110813A2 (en) | 2005-04-12 | 2006-04-12 | Composition and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008537752A true JP2008537752A (ja) | 2008-09-25 |
| JP2008537752A5 JP2008537752A5 (cg-RX-API-DMAC7.html) | 2010-06-17 |
Family
ID=37087668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008506633A Pending JP2008537752A (ja) | 2005-04-12 | 2006-04-12 | がんおよび他の新血管形成疾患を処置するためのＲＮＡｉ治療用の組成物および方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (5) | US7534878B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1877065A4 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2008537752A (cg-RX-API-DMAC7.html) |
| KR (1) | KR20080041145A (cg-RX-API-DMAC7.html) |
| CN (1) | CN101277704A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2006235489A1 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0610499A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2604441A1 (cg-RX-API-DMAC7.html) |
| IL (1) | IL186578A0 (cg-RX-API-DMAC7.html) |
| MX (1) | MX2007012766A (cg-RX-API-DMAC7.html) |
| SG (1) | SG161267A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2006110813A2 (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016535058A (ja) * | 2013-08-07 | 2016-11-10 | アローヘッド ファーマシューティカルズ インコーポレイテッド | 腫瘍細胞へのＲＮＡｉトリガーのインビボ送達のためのポリ結合体 |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2482903A1 (en) | 2002-04-18 | 2003-10-23 | Lynkeus Biotech Gmbh | Means and methods for the specific inhibition of genes in cells and tissue of the cns and/or eye |
| US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| US7951935B2 (en) | 2002-11-14 | 2011-05-31 | Dharmacon, Inc. | siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC) |
| US7612196B2 (en) | 2002-11-14 | 2009-11-03 | Dharmacon, Inc. | siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B) |
| US8198427B1 (en) | 2002-11-14 | 2012-06-12 | Dharmacon, Inc. | SiRNA targeting catenin, beta-1 (CTNNB1) |
| US10011836B2 (en) | 2002-11-14 | 2018-07-03 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| US7635770B2 (en) | 2002-11-14 | 2009-12-22 | Dharmacon, Inc. | siRNA targeting protein kinase N-3 (PKN-3) |
| US7619081B2 (en) | 2002-11-14 | 2009-11-17 | Dharmacon, Inc. | siRNA targeting coatomer protein complex, subunit beta 2 (COPB2) |
| US7691998B2 (en) | 2002-11-14 | 2010-04-06 | Dharmacon, Inc. | siRNA targeting nucleoporin 62kDa (Nup62) |
| US9879266B2 (en) | 2002-11-14 | 2018-01-30 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| US7592442B2 (en) | 2002-11-14 | 2009-09-22 | Dharmacon, Inc. | siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2) |
| US8090542B2 (en) | 2002-11-14 | 2012-01-03 | Dharmacon Inc. | Functional and hyperfunctional siRNA |
| US9719092B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting CNTD2 |
| US9719094B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting SEC61G |
| US9228186B2 (en) | 2002-11-14 | 2016-01-05 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| WO2006006948A2 (en) | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
| US9839649B2 (en) | 2002-11-14 | 2017-12-12 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| US9771586B2 (en) | 2002-11-14 | 2017-09-26 | Thermo Fisher Scientific Inc. | RNAi targeting ZNF205 |
| US7977471B2 (en) | 2002-11-14 | 2011-07-12 | Dharmacon, Inc. | siRNA targeting TNFα |
| AU2004308484A1 (en) | 2003-12-23 | 2005-07-14 | The Trustees Of The University Of Pennsylvania | Compositions and methods for combined therapy of disease |
| US8491914B2 (en) * | 2004-02-13 | 2013-07-23 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (DNL) complexes for delivery of interference RNA |
| US7605250B2 (en) | 2004-05-12 | 2009-10-20 | Dharmacon, Inc. | siRNA targeting cAMP-specific phosphodiesterase 4D |
| US7893244B2 (en) * | 2005-04-12 | 2011-02-22 | Intradigm Corporation | Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases |
| WO2006110813A2 (en) * | 2005-04-12 | 2006-10-19 | Intradigm Corporation | Composition and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| US20070082845A1 (en) * | 2005-07-15 | 2007-04-12 | The Penn State Research Foundation | Ferritin as a therapeutic target in abnormal cells |
| EP1934360A2 (en) * | 2005-10-14 | 2008-06-25 | Nastech Pharmaceutical Company Inc. | Compounds and methods for peptide ribonucleic acid condensate particles for rna therapeutics |
| WO2007080902A1 (ja) * | 2006-01-11 | 2007-07-19 | Kyowa Hakko Kogyo Co., Ltd. | 眼球において標的遺伝子の発現を抑制する組成物および眼球における疾患の治療剤 |
| ES2647452T3 (es) | 2006-08-08 | 2017-12-21 | Rheinische Friedrich-Wilhelms-Universität Bonn | Estructura y uso de oligonucleótidos 5' fosfato |
| WO2008045576A2 (en) * | 2006-10-12 | 2008-04-17 | Yijia Liu | Compositions and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| US20080274121A1 (en) * | 2007-04-30 | 2008-11-06 | Yao James C | Inhibition of Angiogenesis by Mithramycin |
| CN101363027B (zh) * | 2007-08-06 | 2011-07-27 | 武汉大学 | 携带短发夹rna的重组质粒的制备方法及用途 |
| WO2009031671A1 (ja) * | 2007-09-07 | 2009-03-12 | The University Of Tokushima | ｐ５３の発現促進方法およびそれに用いるｐ５３発現促進剤 |
| US20100210710A1 (en) * | 2007-10-12 | 2010-08-19 | Intradigm Corporation | THERAPEUTIC siRNA MOLECULES FOR REDUCING VEGFR1 EXPRESSION IN VITRO AND IN VIVO |
| WO2009061417A1 (en) | 2007-11-06 | 2009-05-14 | Sirnaomics, Inc. | Multi-targeted rnai therapeutics for scarless wound healing of skin |
| EP2215147B1 (en) * | 2007-11-07 | 2014-04-16 | University of Utah Research Foundation | Cleavable modifications to reducible poly(amido ethylenimine)s to enhance nucleotide delivery |
| WO2009108822A1 (en) * | 2008-02-26 | 2009-09-03 | Aparna Biosciences | Engineered tunable nanoparticles for delivery of therapeutics, diagnostics, and experimental compounds and related compositions for therapeutic use |
| ES2338400B1 (es) * | 2008-05-06 | 2011-09-14 | David Benet Ferrus | Conjunto de moleculas antiangiogenicas y su uso. |
| EP2297323A1 (en) | 2008-05-21 | 2011-03-23 | Hartmann, Gunther | 5' triphosphate oligonucleotide with blunt end and uses thereof |
| WO2009151539A1 (en) * | 2008-05-24 | 2009-12-17 | Sirnaomics, Inc. | COMPOSITIONS AND METHODS USING siRNA MOLECULES FOR TREATMENT OF GLIOMAS |
| CA2745832A1 (en) | 2008-12-04 | 2010-06-10 | Opko Ophthalmics, Llc | Compositions and methods for selective inhibition of pro-angiogenic vegf isoforms |
| US9012622B2 (en) | 2008-12-31 | 2015-04-21 | Patrick Y. Lu | Compositions and methods using siRNA molecules and siRNA cocktails for the treatment of breast cancer |
| DE102009006606A1 (de) * | 2009-01-29 | 2010-08-05 | Philipps-Universität Marburg | Nicht-virales Transfektionsmittel |
| US20120114710A1 (en) * | 2009-05-18 | 2012-05-10 | Lynn Kirkpatrick | Carbon nanotubes complexed with multiple bioactive agents and methods related thereto |
| WO2011011061A2 (en) * | 2009-07-21 | 2011-01-27 | The Board Of Trustees Of The Leland Stanford Junior University | Method of regulating angiogenesis and lymphangiogenesis, and a pharmaceutical composition for effecting anti-angiogenic and anti-lymphangiogenic cancer therapy |
| WO2011039646A2 (en) | 2009-09-30 | 2011-04-07 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Papilloma virus -like particles for targeted gene delivery |
| EP2549986B1 (en) * | 2010-03-24 | 2019-10-30 | Northeastern University | Multi-compartmental macrophage delivery |
| WO2011120053A1 (en) | 2010-03-26 | 2011-09-29 | Mersana Therapeutics, Inc. | Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof |
| US9642873B2 (en) | 2010-05-04 | 2017-05-09 | Sirnaomics, Inc. | Combinations of TGFβ and COX-2 inhibitors and methods for their therapeutic application |
| WO2012016139A2 (en) | 2010-07-29 | 2012-02-02 | Sirnaomics, Inc. | Sirna compositions and methods for treatment of hpv and other infections |
| EP2508530A1 (en) | 2011-03-28 | 2012-10-10 | Rheinische Friedrich-Wilhelms-Universität Bonn | Purification of triphosphorylated oligonucleotides using capture tags |
| CN102727513B (zh) * | 2011-04-15 | 2014-07-09 | 百奥迈科生物技术有限公司 | 靶向于组织因子基因的小核酸及其用途 |
| US20120301537A1 (en) * | 2011-05-23 | 2012-11-29 | Delta-Fly Pharma, Inc. | LIPOSOME CONTAINING shRNA MOLECULE TARGETING A THYMIDYLATE SYNTHASE AND USE THEREOF |
| US8592572B2 (en) * | 2011-05-23 | 2013-11-26 | Delta-Fly Pharma, Inc. | Liposome containing shRNA molecule targeting a thymidylate synthase and use thereof |
| US9717792B2 (en) | 2012-02-02 | 2017-08-01 | The University Of British Columbia | Combination therapy for cancer using HSP27 inhibitor and EGFR tyrosine kinase inhibitors or anti-folates |
| EP2712870A1 (en) | 2012-09-27 | 2014-04-02 | Rheinische Friedrich-Wilhelms-Universität Bonn | Novel RIG-I ligands and methods for producing them |
| US9801953B2 (en) | 2012-10-15 | 2017-10-31 | Emory University | Nanoparticles carrying nucleic acid cassettes for expressing RNA |
| US9228189B2 (en) | 2012-10-26 | 2016-01-05 | Geron Corporation | C-myc antisense oligonucleotides and methods for using the same to treat cell-proliferative disorders |
| CN104635967B (zh) * | 2013-11-12 | 2018-04-10 | 宸鸿光电科技股份有限公司 | 有机发光二极管触控显示设备 |
| WO2015148247A1 (en) * | 2014-03-24 | 2015-10-01 | Shire Human Genetic Therapies, Inc. | Mrna therapy for the treatment of ocular diseases |
| EP3265107B1 (en) | 2015-03-02 | 2024-10-02 | 180 Therapeutics LP | Method of treating a localized fibrotic disorder using a tnf receptor 2 antagonist |
| EP3548005A4 (en) | 2016-11-29 | 2020-06-17 | Puretech Health LLC | Exosomes for delivery of therapeutic agents |
| GB201904337D0 (en) * | 2019-03-28 | 2019-05-15 | Sisaf Ltd | A delivery system |
| CN111298129B (zh) * | 2019-08-28 | 2023-05-09 | 中国人民解放军陆军军医大学第二附属医院 | 二甲双胍介导核酸纳米材料自组装方法及采用该方法制备的纳米制剂和应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004028471A2 (en) * | 2002-09-28 | 2004-04-08 | Massachusetts Institute Of Technology | Influenza therapeutic |
| WO2005019453A2 (en) * | 2001-05-18 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA) |
Family Cites Families (86)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5240848A (en) * | 1988-11-21 | 1993-08-31 | Monsanto Company | Dna sequences encoding human vascular permeability factor having 189 amino acids |
| US5332671A (en) * | 1989-05-12 | 1994-07-26 | Genetech, Inc. | Production of vascular endothelial cell growth factor and DNA encoding same |
| US5726152A (en) * | 1990-09-21 | 1998-03-10 | Merck & Co., Inc. | Vascular endothelial cell growth factor II |
| CA2064331C (en) * | 1991-03-28 | 2003-02-18 | Marvin L. Bayne | Vascular endothelial cell growth factor c subunit |
| US6710174B2 (en) | 2001-09-13 | 2004-03-23 | Isis Pharmaceuticals, Inc. | Antisense inhibition of vascular endothelial growth factor receptor-1 expression |
| US6743909B2 (en) * | 2002-06-17 | 2004-06-01 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTPN12 expression |
| US6037329A (en) * | 1994-03-15 | 2000-03-14 | Selective Genetics, Inc. | Compositions containing nucleic acids and ligands for therapeutic treatment |
| US6150092A (en) * | 1994-06-27 | 2000-11-21 | Taogosei Company, Ltd. | Antisense nucleic acid compound targeted to VEGF |
| AU3374795A (en) | 1994-08-29 | 1996-03-22 | Prizm Pharmaceuticals, Inc. | Conjugates of vascular endothelial growth factor with targeted agents |
| WO1996020403A1 (en) | 1994-12-23 | 1996-07-04 | Ludwig Institute For Cancer Research | Assay, receptor proteins and ligands |
| US5928939A (en) * | 1995-03-01 | 1999-07-27 | Ludwig Institute For Cancer Research | Vascular endothelial growth factor-b and dna coding therefor |
| US5607918A (en) * | 1995-03-01 | 1997-03-04 | Ludwig Institute For Cancer Research | Vascular endothelial growth factor-B and DNA coding therefor |
| WO1997006814A1 (en) * | 1995-08-15 | 1997-02-27 | Connective Therapeutics, Inc. | Method of promoting angiogenesis |
| US7005505B1 (en) * | 1995-08-25 | 2006-02-28 | Genentech, Inc. | Variants of vascular endothelial cell growth factor |
| US6346398B1 (en) | 1995-10-26 | 2002-02-12 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for the treatment of diseases or conditions related to levels of vascular endothelial growth factor receptor |
| US20040142895A1 (en) * | 1995-10-26 | 2004-07-22 | Sirna Therapeutics, Inc. | Nucleic acid-based modulation of gene expression in the vascular endothelial growth factor pathway |
| US6013780A (en) * | 1996-09-06 | 2000-01-11 | Technion Research & Development Co. Ltd. | VEGF145 expression vectors |
| EP1426444A3 (en) | 1996-09-06 | 2004-06-16 | Technion Research & Development Co., Ltd. | Use of the angiogenic factor VEGF145 in treating cardiovascular diseases |
| US6750044B1 (en) * | 1996-10-17 | 2004-06-15 | Genentech, Inc. | Variants of vascular endothelial cell growth factor having antagonistic properties, nucleic acids encoding the same and host cells comprising those nucleic acids |
| US6485942B1 (en) * | 1997-02-14 | 2002-11-26 | Genentech, Inc. | Variants of vascular endothelial cell growth factor having altered pharmacological properties, and recombinant methods of production |
| US6395707B1 (en) * | 1997-02-14 | 2002-05-28 | Genentech, Inc. | Methods of treatment utilizing variants of vascular endothelial cell growth factor |
| US6479729B1 (en) * | 1998-02-06 | 2002-11-12 | The Johns Hopkins University | Mouse model for ocular neovascularization |
| US6479654B1 (en) * | 1998-02-06 | 2002-11-12 | Collateral Therapeutics | Forms of the angiogenic factor vascular endothelial cell growth factor: VEGF |
| US6783961B1 (en) * | 1999-02-26 | 2004-08-31 | Genset S.A. | Expressed sequence tags and encoded human proteins |
| WO1999063975A2 (en) | 1998-06-10 | 1999-12-16 | Biognostik Gesellschaft für Biomolekulare Diagnostik mbH | A method for stimulating the immune system |
| AU4438399A (en) | 1998-06-11 | 1999-12-30 | University Of Medicine And Dentistry Of New Jersey | Wound treatment through inhibition of adenosine diphosphate ribosyl transferase |
| EP0979869A1 (en) * | 1998-08-07 | 2000-02-16 | Hoechst Marion Roussel Deutschland GmbH | Short oligonucleotides for the inhibition of VEGF expression |
| US7030083B2 (en) * | 1998-09-09 | 2006-04-18 | University Of Washington | Treatment of eclampsia and preeclampsia |
| PT1109571E (pt) * | 1998-09-09 | 2004-05-31 | Scios Inc | Metodos de tratamento da hipertensao e composicoes para utilizacao nesses metodos |
| US6677300B1 (en) * | 1998-09-09 | 2004-01-13 | Scios, Inc. | Treatment of microvascular angiopathies |
| EP1417971A3 (en) | 1998-09-09 | 2004-06-30 | Scios Inc. | Use of an angiogenic factor for the treatment of microvascular angiopathies |
| US6916915B1 (en) * | 1998-11-20 | 2005-07-12 | Duke University | Stressor regulated genes |
| CA2296792A1 (en) | 1999-02-26 | 2000-08-26 | Genset S.A. | Expressed sequence tags and encoded human proteins |
| IL128852A0 (en) * | 1999-03-05 | 2000-01-31 | Compugen Ltd | Novel nucleic acid and amino acid sequences |
| US6783954B2 (en) * | 1999-03-05 | 2004-08-31 | Compugen Ltd. | VEGF nucleic acid and amino acid sequences |
| DE19910419A1 (de) | 1999-03-10 | 2000-09-21 | Aventis Pharma Gmbh | Zielzellspezifische, multivalente Proteine (MVP) |
| US6943153B1 (en) * | 1999-03-15 | 2005-09-13 | The Regents Of The University Of California | Use of recombinant gene delivery vectors for treating or preventing diseases of the eye |
| WO2000071713A1 (en) * | 1999-05-20 | 2000-11-30 | Scios Inc. | Vascular endothelial growth factor variants |
| US6187822B1 (en) * | 1999-06-11 | 2001-02-13 | University Of Medicine & Dentistry Of Nj | Wound treatment through inhibition of adenosine diphosphate ribosyl transferase |
| WO2001027292A2 (en) | 1999-10-08 | 2001-04-19 | Biofocus Discovery Limited | Methods and compositions for targeting a cell |
| US6770633B1 (en) * | 1999-10-26 | 2004-08-03 | Immusol, Inc. | Ribozyme therapy for the treatment of proliferative skin and eye diseases |
| US7078382B1 (en) * | 1999-11-02 | 2006-07-18 | Genentech, Inc. | Modulation of eNOS activity and therapeutic uses thereof |
| EP1564292A1 (en) * | 2000-01-19 | 2005-08-17 | Parkash S. Gill | Pharmaceutical compositions and methods of treatment based on VEGF antisense oligonucleotides |
| CA2397200C (en) | 2000-02-09 | 2010-11-23 | Connetics Corporation | Use of relaxin to treat diseases related to vasoconstriction |
| DE60131146T2 (de) * | 2000-02-25 | 2008-03-06 | Ludwig Institute For Cancer Research | Material und verfahren die hybridvaskularendothelwachstumfaktoren dns und proteine enthalten und screeningverfahren für modulatoren |
| US6974667B2 (en) * | 2000-06-14 | 2005-12-13 | Gene Logic, Inc. | Gene expression profiles in liver cancer |
| US6727066B2 (en) * | 2000-07-28 | 2004-04-27 | Incyte Corporation | Genes expressed in treated human C3A liver cell cultures |
| US6673549B1 (en) * | 2000-10-12 | 2004-01-06 | Incyte Corporation | Genes expressed in C3A liver cell cultures treated with steroids |
| WO2002031141A2 (en) | 2000-10-13 | 2002-04-18 | Institut De Cardiologie De Montreal | Antisense oligonucleotide directed toward mammalian vegf receptor genes and uses thereof |
| WO2002085309A2 (en) | 2001-04-24 | 2002-10-31 | Epigenesis Pharmaceuticals, Inc. | Composition, formulations & kits for treatment of respiratory & lung disease with anti-sense oligonucleotides & a bronchodilating agent |
| WO2002085308A2 (en) | 2001-04-24 | 2002-10-31 | Epigenesis Pharmaceuticals, Inc. | Antisense and anti-inflammatory based compositions to treat respiratory disorders |
| US7517864B2 (en) | 2001-05-18 | 2009-04-14 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| WO2004111237A1 (en) | 2003-04-16 | 2004-12-23 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF PLATELET-DERIVED ENDOTHELIAL CELL GROWTH FACTOR (ECGF1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US20050148530A1 (en) * | 2002-02-20 | 2005-07-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US20050222066A1 (en) * | 2001-05-18 | 2005-10-06 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| WO2003070910A2 (en) | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND VEGF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| EP1262199A1 (en) | 2001-05-23 | 2002-12-04 | Fornix Biosciences N.V. | Vectors for enhanced expression of VEGF for disease treatment |
| CA2448320A1 (en) | 2001-05-29 | 2002-12-05 | Sirna Therapeutics, Inc. | Ribozyme based treatment of female reproductive diseases |
| WO2003007889A2 (en) * | 2001-07-17 | 2003-01-30 | Research Development Foundation | Therapeutic agents comprising pro-apoptotic proteins |
| EP1293569A3 (en) | 2001-09-14 | 2004-03-31 | Research Association for Biotechnology | Full-length cDNAs |
| JP2003088388A (ja) * | 2001-09-14 | 2003-03-25 | Herikkusu Kenkyusho:Kk | 新規な全長ｃＤＮＡ |
| JP2005508396A (ja) * | 2001-11-02 | 2005-03-31 | イントラディグム、コーポレイション | 核酸送達ビヒクルのための治療方法 |
| FR2832154B1 (fr) | 2001-11-09 | 2007-03-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene |
| US20050075304A1 (en) * | 2001-11-30 | 2005-04-07 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US6927779B2 (en) * | 2002-05-13 | 2005-08-09 | Large Scale Biology Corporation | Web-based well plate information retrieval and display system |
| US7148342B2 (en) * | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| US8090542B2 (en) | 2002-11-14 | 2012-01-03 | Dharmacon Inc. | Functional and hyperfunctional siRNA |
| FR2835837B1 (fr) | 2003-02-06 | 2007-03-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leurs utilisation pour reprimer specifiquement un gene codant pour un facteur de croissance |
| FR2835838B1 (fr) | 2003-02-06 | 2007-11-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene codant pour un facteur de transcription |
| JP2006522158A (ja) * | 2003-04-03 | 2006-09-28 | アルナイラム ファーマシューティカルズ インコーポレイテッド | ｉＲＮＡ複合体 |
| US20050096370A1 (en) | 2003-04-07 | 2005-05-05 | Bizbiotech Co., Ltd. | Method for inhibiting tumor angiogenesis and tumor growth |
| DE10316701A1 (de) | 2003-04-09 | 2004-11-04 | Hinzmann, Bernd, Dr. | Humane Nukleinsäuresequenzen aus Bronchialkarzinomen |
| US20050019927A1 (en) * | 2003-07-13 | 2005-01-27 | Markus Hildinger | DECREASING GENE EXPRESSION IN A MAMMALIAN SUBJECT IN VIVO VIA AAV-MEDIATED RNAi EXPRESSION CASSETTE TRANSFER |
| EP1548445A3 (en) | 2003-12-22 | 2005-11-23 | F. Hoffmann-La Roche Ag | Novel targets for obesity from fat tissue |
| CN101044152A (zh) * | 2004-02-05 | 2007-09-26 | 因特拉迪格姆公司 | 组合RNAi治疗的方法和组合物 |
| CA2555335A1 (en) * | 2004-02-05 | 2005-08-25 | Intradigm Corporation | Rnai therapeutics for treatment of eye neovascularization diseases |
| EP2899278A1 (en) * | 2004-03-12 | 2015-07-29 | Alnylam Pharmaceuticals Inc. | iRNA agents targeting VEGF |
| CN101052717A (zh) * | 2004-05-11 | 2007-10-10 | α基因株式会社 | 诱发rna干扰的多核苷酸以及使用该多核苷酸的基因表达抑制方法 |
| EP1607485A1 (en) | 2004-06-14 | 2005-12-21 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Method for quantifying VEGF121 isoform in a biological sample |
| CA2587962A1 (en) * | 2004-11-17 | 2006-06-08 | University Of Maryland, Baltimore | Highly branched hk peptides as effective carriers of sirna |
| WO2006110813A2 (en) * | 2005-04-12 | 2006-10-19 | Intradigm Corporation | Composition and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| US7893244B2 (en) * | 2005-04-12 | 2011-02-22 | Intradigm Corporation | Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases |
| EP1714970A1 (en) | 2005-04-22 | 2006-10-25 | Universität des Saarlandes | Use of inhibitors of RNAse A-family enzymes for stabilizing oligonucleotides having RNA interfering activity |
| CN100374573C (zh) | 2006-04-14 | 2008-03-12 | 中国医学科学院医药生物技术研究所 | 一种可稳定表达VEGF shRNA的载体pCD-VEGF |
| WO2008045576A2 (en) | 2006-10-12 | 2008-04-17 | Yijia Liu | Compositions and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| US20100210710A1 (en) | 2007-10-12 | 2010-08-19 | Intradigm Corporation | THERAPEUTIC siRNA MOLECULES FOR REDUCING VEGFR1 EXPRESSION IN VITRO AND IN VIVO |
-
2006
- 2006-04-12 WO PCT/US2006/013645 patent/WO2006110813A2/en not_active Ceased
- 2006-04-12 EP EP06749877A patent/EP1877065A4/en not_active Withdrawn
- 2006-04-12 BR BRPI0610499-1A patent/BRPI0610499A2/pt not_active IP Right Cessation
- 2006-04-12 KR KR1020077026255A patent/KR20080041145A/ko not_active Withdrawn
- 2006-04-12 CA CA002604441A patent/CA2604441A1/en not_active Abandoned
- 2006-04-12 MX MX2007012766A patent/MX2007012766A/es not_active Application Discontinuation
- 2006-04-12 CN CNA2006800190118A patent/CN101277704A/zh active Pending
- 2006-04-12 AU AU2006235489A patent/AU2006235489A1/en not_active Abandoned
- 2006-04-12 SG SG201002548-4A patent/SG161267A1/en unknown
- 2006-04-12 JP JP2008506633A patent/JP2008537752A/ja active Pending
-
2007
- 2007-06-29 US US11/824,085 patent/US7534878B2/en not_active Expired - Fee Related
- 2007-06-29 US US11/824,426 patent/US7723316B2/en not_active Expired - Fee Related
- 2007-06-29 US US11/824,084 patent/US7893243B2/en not_active Expired - Fee Related
- 2007-08-20 US US11/894,567 patent/US20080153771A1/en not_active Abandoned
- 2007-10-11 IL IL186578A patent/IL186578A0/en unknown
-
2009
- 2009-04-09 US US12/420,907 patent/US7786092B2/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005019453A2 (en) * | 2001-05-18 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA) |
| WO2004028471A2 (en) * | 2002-09-28 | 2004-04-08 | Massachusetts Institute Of Technology | Influenza therapeutic |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016535058A (ja) * | 2013-08-07 | 2016-11-10 | アローヘッド ファーマシューティカルズ インコーポレイテッド | 腫瘍細胞へのＲＮＡｉトリガーのインビボ送達のためのポリ結合体 |
Also Published As
| Publication number | Publication date |
|---|---|
| MX2007012766A (es) | 2008-10-01 |
| IL186578A0 (en) | 2008-01-20 |
| US20080153771A1 (en) | 2008-06-26 |
| KR20080041145A (ko) | 2008-05-09 |
| WO2006110813A3 (en) | 2007-11-15 |
| US7893243B2 (en) | 2011-02-22 |
| CA2604441A1 (en) | 2006-10-19 |
| US20080220027A1 (en) | 2008-09-11 |
| CN101277704A (zh) | 2008-10-01 |
| US7723316B2 (en) | 2010-05-25 |
| AU2006235489A1 (en) | 2006-10-19 |
| WO2006110813A2 (en) | 2006-10-19 |
| BRPI0610499A2 (pt) | 2010-06-22 |
| US7786092B2 (en) | 2010-08-31 |
| US7534878B2 (en) | 2009-05-19 |
| EP1877065A2 (en) | 2008-01-16 |
| EP1877065A4 (en) | 2010-12-22 |
| SG161267A1 (en) | 2010-05-27 |
| US20080241198A1 (en) | 2008-10-02 |
| US20090227657A1 (en) | 2009-09-10 |
| US20090118208A1 (en) | 2009-05-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2008537752A (ja) | がんおよび他の新血管形成疾患を処置するためのＲＮＡｉ治療用の組成物および方法 | |
| JP2008537752A5 (cg-RX-API-DMAC7.html) | ||
| US7893244B2 (en) | Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases | |
| Guo et al. | ICAM-1-targeted, Lcn2 siRNA-encapsulating liposomes are potent anti-angiogenic agents for triple negative breast cancer | |
| Wei et al. | Brain tumor-targeted therapy by systemic delivery of siRNA with Transferrin receptor-mediated core-shell nanoparticles | |
| Lee et al. | Co-delivery of VEGF and Bcl-2 dual-targeted siRNA polymer using a single nanoparticle for synergistic anti-cancer effects in vivo | |
| Lee et al. | Recent developments in nanoparticle‐based siRNA delivery for cancer therapy | |
| Miele et al. | Nanoparticle-based delivery of small interfering RNA: challenges for cancer therapy | |
| US8541568B2 (en) | Compositions and methods using siRNA molecules for treatment of gliomas | |
| Dong et al. | Therapeutic potential of targeted multifunctional nanocomplex co-delivery of siRNA and low-dose doxorubicin in breast cancer | |
| Wang et al. | Targeted delivery of tumor suppressor microRNA-1 by transferrin-conjugated lipopolyplex nanoparticles to patient-derived glioblastoma stem cells | |
| JP2007528899A (ja) | 受容体特異的ナノ容器を使用するショートヘアピンｒｎａをコードする遺伝子の送達 | |
| Polyak et al. | Systemic delivery of siRNA by aminated poly (α) glutamate for the treatment of solid tumors | |
| US20130259927A1 (en) | Ewing's Sarcoma Bifunctional shRNA Design | |
| US8361510B2 (en) | Nanogels for cellular delivery of therapeutics | |
| Wang et al. | Rational design of multimodal therapeutic nanosystems for effective inhibition of tumor growth and metastasis | |
| Gujrati et al. | Targeted systemic delivery of therapeutic siRNA | |
| Shim et al. | Small interfering RNAs (siRNAs) as cancer therapeutics | |
| HK1127276A (en) | Composition and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases | |
| Teymouri et al. | Non-viral siRNA delivery systems for pancreatic cancer therapy | |
| Rodriguez‐Aguayo et al. | RNAi in cancer therapy | |
| Schilb | Optimization of Non-Viral Gene Delivery System for Image-Guided Therapy for Triple Negative Breast Cancer | |
| Wang | Design of multifunctional nanomaterials to improve cancer gene therapy | |
| ALSHAER | L’UNIVERSITE PARIS-SACLAY | |
| Philippou et al. | DEVELOPING APTAMERS FOR THE DELIVERY OF THERAPEUTIC RNA |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090410 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100409 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120223 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120817 |