JP2011529912A5 - - Google Patents

Info

Publication number

JP2011529912A5

JP2011529912A5 JP2011521353A JP2011521353A JP2011529912A5 JP 2011529912 A5 JP2011529912 A5 JP 2011529912A5 JP 2011521353 A JP2011521353 A JP 2011521353A JP 2011521353 A JP2011521353 A JP 2011521353A JP 2011529912 A5 JP2011529912 A5 JP 2011529912A5

Authority

JP

Japan

Prior art keywords

peg

lipid

cholesterol

nanoparticle

oligonucleotide

Prior art date

2009-07-31

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

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• 239000002105 nanoparticle Substances 0.000 claims 27
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 22
• 239000000203 mixture Substances 0.000 claims 15
• 108091034117 Oligonucleotide Proteins 0.000 claims 11
• 235000012000 cholesterol Nutrition 0.000 claims 11
• 150000002632 lipids Chemical class 0.000 claims 10
• -1 cationic lipid Chemical class 0.000 claims 9
• 210000004027 cell Anatomy 0.000 claims 6
• 125000002091 cationic group Chemical group 0.000 claims 5
• 108020004707 nucleic acids Proteins 0.000 claims 5
• 102000039446 nucleic acids Human genes 0.000 claims 5
• 150000007523 nucleic acids Chemical class 0.000 claims 5
• 239000008194 pharmaceutical composition Substances 0.000 claims 5
• JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims 4
• 206010028980 Neoplasm Diseases 0.000 claims 4
• 230000000692 anti-sense effect Effects 0.000 claims 4
• 201000011510 cancer Diseases 0.000 claims 4
• 150000008104 phosphatidylethanolamines Chemical class 0.000 claims 4
• 108090000623 proteins and genes Proteins 0.000 claims 4
• YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 claims 3
• 125000000217 alkyl group Chemical group 0.000 claims 3
• 229940106189 ceramide Drugs 0.000 claims 3
• ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 claims 3
• 230000000799 fusogenic effect Effects 0.000 claims 3
• 230000014509 gene expression Effects 0.000 claims 3
• 229910052739 hydrogen Inorganic materials 0.000 claims 3
• 239000001257 hydrogen Substances 0.000 claims 3
• 238000000034 method Methods 0.000 claims 3
• VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 claims 3
• 108091023037 Aptamer Proteins 0.000 claims 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
• 108700011259 MicroRNAs Proteins 0.000 claims 2
• CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 claims 2
• 108091093037 Peptide nucleic acid Proteins 0.000 claims 2
• 108020004459 Small interfering RNA Proteins 0.000 claims 2
• 210000005260 human cell Anatomy 0.000 claims 2
• 238000000338 in vitro Methods 0.000 claims 2
• 239000002679 microRNA Substances 0.000 claims 2
• 239000004055 small Interfering RNA Substances 0.000 claims 2
• NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims 1
• 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 claims 1
• 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 claims 1
• 108060000903 Beta-catenin Proteins 0.000 claims 1
• 102000015735 Beta-catenin Human genes 0.000 claims 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims 1
• 108090000994 Catalytic RNA Proteins 0.000 claims 1
• 102000053642 Catalytic RNA Human genes 0.000 claims 1
• 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 claims 1
• 108700020796 Oncogene Proteins 0.000 claims 1
• 108091030071 RNAI Proteins 0.000 claims 1
• 108091028664 Ribonucleotide Proteins 0.000 claims 1
• 108010002687 Survivin Proteins 0.000 claims 1
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 1
• 239000002246 antineoplastic agent Substances 0.000 claims 1
• 230000004663 cell proliferation Effects 0.000 claims 1
• 229940127089 cytotoxic agent Drugs 0.000 claims 1
• 230000009368 gene silencing by RNA Effects 0.000 claims 1
• 150000002431 hydrogen Chemical class 0.000 claims 1
• 239000012678 infectious agent Substances 0.000 claims 1
• 230000002401 inhibitory effect Effects 0.000 claims 1
• 210000004185 liver Anatomy 0.000 claims 1
• 230000001394 metastastic effect Effects 0.000 claims 1
• 206010061289 metastatic neoplasm Diseases 0.000 claims 1
• 230000037361 pathway Effects 0.000 claims 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims 1
• 230000004647 pro-inflammatory pathway Effects 0.000 claims 1
• 230000006482 proangiogenic pathway Effects 0.000 claims 1
• 230000035755 proliferation Effects 0.000 claims 1
• 239000002336 ribonucleotide Substances 0.000 claims 1
• 125000002652 ribonucleotide group Chemical group 0.000 claims 1
• 108091092562 ribozyme Proteins 0.000 claims 1
• 230000003612 virological effect Effects 0.000 claims 1
• 0 CC(*)(*)C(*)(*CCC1)C1(*)N(*)CCC* Chemical compound CC(*)(*)C(*)(*CCC1)C1(*)N(*)CCC* 0.000 description 5
• MZQUWCQHUCBQSW-UHFFFAOYSA-N IN1C(CCC2)N2CCC1 Chemical compound IN1C(CCC2)N2CCC1 MZQUWCQHUCBQSW-UHFFFAOYSA-N 0.000 description 1