JP2014511173A - 選択的細胞殺滅のための生物学的有効ヌクレオチド分子、その使用及び適用キット - Google Patents
選択的細胞殺滅のための生物学的有効ヌクレオチド分子、その使用及び適用キット Download PDFInfo
- Publication number
- JP2014511173A JP2014511173A JP2013549831A JP2013549831A JP2014511173A JP 2014511173 A JP2014511173 A JP 2014511173A JP 2013549831 A JP2013549831 A JP 2013549831A JP 2013549831 A JP2013549831 A JP 2013549831A JP 2014511173 A JP2014511173 A JP 2014511173A
- Authority
- JP
- Japan
- Prior art keywords
- cells
- biologically effective
- cell
- nucleotide molecule
- mrna
- 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
- 125000003729 nucleotide group Chemical group 0.000 title claims abstract description 55
- 239000002773 nucleotide Substances 0.000 title claims abstract description 52
- 230000022534 cell killing Effects 0.000 title claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims abstract description 78
- 108020004999 messenger RNA Proteins 0.000 claims abstract description 60
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 45
- 230000000694 effects Effects 0.000 claims abstract description 26
- 230000002147 killing effect Effects 0.000 claims abstract description 6
- 230000002538 fungal effect Effects 0.000 claims abstract description 3
- 108020004459 Small interfering RNA Proteins 0.000 claims description 45
- 239000003708 ampul Substances 0.000 claims description 14
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 13
- -1 CAGG Proteins 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 239000002105 nanoparticle Substances 0.000 claims description 5
- 238000001890 transfection Methods 0.000 claims description 5
- 229920002873 Polyethylenimine Polymers 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 4
- 230000003938 response to stress Effects 0.000 claims description 4
- 231100000331 toxic Toxicity 0.000 claims description 4
- 230000002588 toxic effect Effects 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 108020004414 DNA Proteins 0.000 claims description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 3
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 108010052418 (N-(2-((4-((2-((4-(9-acridinylamino)phenyl)amino)-2-oxoethyl)amino)-4-oxobutyl)amino)-1-(1H-imidazol-4-ylmethyl)-1-oxoethyl)-6-(((-2-aminoethyl)amino)methyl)-2-pyridinecarboxamidato) iron(1+) Proteins 0.000 claims description 2
- DZIKSWKAPREDIH-WDTGYIAMSA-N 3-[(3s,5s,8r,9s,10s,13r,17r)-3-[(2r,3r,4s,5s,6r)-3-[(4r,5s,6r)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-14-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2h-fur Chemical compound C1[C@@H](O)[C@H](O)[C@@H](C)OC1O[C@H]1[C@H](O[C@@H]2C[C@H]3[C@]([C@@H]4[C@H](C5(CC[C@@H]([C@@]5(C)CC4)C=4COC(=O)C=4)O)CC3)(C)CC2)O[C@H](CO)[C@@H](O)[C@@H]1O DZIKSWKAPREDIH-WDTGYIAMSA-N 0.000 claims description 2
- 102100039217 3-ketoacyl-CoA thiolase, peroxisomal Human genes 0.000 claims description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 2
- 102100032091 ALK and LTK ligand 2 Human genes 0.000 claims description 2
- VWEWCZSUWOEEFM-WDSKDSINSA-N Ala-Gly-Ala-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(O)=O VWEWCZSUWOEEFM-WDSKDSINSA-N 0.000 claims description 2
- 101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 claims description 2
- 241001463143 Auca Species 0.000 claims description 2
- 241000196324 Embryophyta Species 0.000 claims description 2
- RTDFOQVLLJZRIH-JZAVHCKJSA-N Glycoursocholanic acid Chemical compound C([C@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)CC1 RTDFOQVLLJZRIH-JZAVHCKJSA-N 0.000 claims description 2
- 102100033969 Guanylyl cyclase-activating protein 1 Human genes 0.000 claims description 2
- 101100153048 Homo sapiens ACAA1 gene Proteins 0.000 claims description 2
- 101000776351 Homo sapiens ALK and LTK ligand 2 Proteins 0.000 claims description 2
- 101001068480 Homo sapiens Guanylyl cyclase-activating protein 1 Proteins 0.000 claims description 2
- 101001128634 Homo sapiens NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial Proteins 0.000 claims description 2
- 101000869690 Homo sapiens Protein S100-A8 Proteins 0.000 claims description 2
- PKFBJSDMCRJYDC-GEZSXCAASA-N N-acetyl-s-geranylgeranyl-l-cysteine Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CSC[C@@H](C(O)=O)NC(C)=O PKFBJSDMCRJYDC-GEZSXCAASA-N 0.000 claims description 2
- 102100032194 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial Human genes 0.000 claims description 2
- 102100029812 Protein S100-A12 Human genes 0.000 claims description 2
- 101710110949 Protein S100-A12 Proteins 0.000 claims description 2
- 102100032442 Protein S100-A8 Human genes 0.000 claims description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims description 2
- 239000013024 dilution buffer Substances 0.000 claims description 2
- CJWXCNXHAIFFMH-AVZHFPDBSA-N n-[(2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5r)-2-acetamido-4,5,6-trihydroxy-1-oxohexan-3-yl]oxy-3,5-dihydroxy-6-methyloxan-4-yl]acetamide Chemical compound C[C@H]1O[C@@H](O[C@@H]([C@@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O)[C@H](O)[C@@H](NC(C)=O)[C@@H]1O CJWXCNXHAIFFMH-AVZHFPDBSA-N 0.000 claims description 2
- 210000001236 prokaryotic cell Anatomy 0.000 claims description 2
- 239000011535 reaction buffer Substances 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims 2
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims 2
- 241000023308 Acca Species 0.000 claims 1
- 210000004102 animal cell Anatomy 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 230000007810 virus-infected cell apoptotic process Effects 0.000 claims 1
- 230000014509 gene expression Effects 0.000 abstract description 18
- 238000000034 method Methods 0.000 abstract description 13
- 239000000126 substance Substances 0.000 abstract description 6
- 210000004881 tumor cell Anatomy 0.000 abstract description 4
- 238000003782 apoptosis assay Methods 0.000 abstract description 2
- 230000006907 apoptotic process Effects 0.000 abstract description 2
- 230000005522 programmed cell death Effects 0.000 abstract description 2
- 239000004055 small Interfering RNA Substances 0.000 description 42
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 7
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 5
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 101001111984 Homo sapiens N-acylneuraminate-9-phosphatase Proteins 0.000 description 4
- 102100023906 N-acylneuraminate-9-phosphatase Human genes 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000009437 off-target effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 102100030886 Complement receptor type 1 Human genes 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
- 101000727061 Homo sapiens Complement receptor type 1 Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010048999 Transcription Factor 3 Proteins 0.000 description 3
- 102100038313 Transcription factor E2-alpha Human genes 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 3
- 230000009368 gene silencing by RNA Effects 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- KQPKMEYBZUPZGK-UHFFFAOYSA-N 4-[(4-azido-2-nitroanilino)methyl]-5-(hydroxymethyl)-2-methylpyridin-3-ol Chemical compound CC1=NC=C(CO)C(CNC=2C(=CC(=CC=2)N=[N+]=[N-])[N+]([O-])=O)=C1O KQPKMEYBZUPZGK-UHFFFAOYSA-N 0.000 description 2
- 102100027221 CD81 antigen Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 102100033369 Glutathione S-transferase A4 Human genes 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 101000914479 Homo sapiens CD81 antigen Proteins 0.000 description 2
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108091030071 RNAI Proteins 0.000 description 2
- 101150045565 Socs1 gene Proteins 0.000 description 2
- 108700027336 Suppressor of Cytokine Signaling 1 Proteins 0.000 description 2
- 102100024779 Suppressor of cytokine signaling 1 Human genes 0.000 description 2
- 102100022300 Transmembrane protein 215 Human genes 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000011242 molecular targeted therapy Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000001082 somatic cell Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VUFNLQXQSDUXKB-DOFZRALJSA-N 2-[4-[4-[bis(2-chloroethyl)amino]phenyl]butanoyloxy]ethyl (5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)OCCOC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 VUFNLQXQSDUXKB-DOFZRALJSA-N 0.000 description 1
- 101150090724 3 gene Proteins 0.000 description 1
- 101150033839 4 gene Proteins 0.000 description 1
- 101150096316 5 gene Proteins 0.000 description 1
- 101150039504 6 gene Proteins 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010048998 Acute phase reaction Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102100035353 Cyclin-dependent kinase 2-associated protein 1 Human genes 0.000 description 1
- 241001050985 Disco Species 0.000 description 1
- 101100170539 Drosophila melanogaster disco gene Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000002494 Endoribonucleases Human genes 0.000 description 1
- 108010093099 Endoribonucleases Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241001123946 Gaga Species 0.000 description 1
- 101710193825 Glutathione S-transferase alpha-4 Proteins 0.000 description 1
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 1
- 108010024164 HLA-G Antigens Proteins 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000805876 Homo sapiens Disco-interacting protein 2 homolog A Proteins 0.000 description 1
- 101000870514 Homo sapiens Glutathione S-transferase A4 Proteins 0.000 description 1
- 101001134943 Homo sapiens Protocadherin alpha-9 Proteins 0.000 description 1
- 101001129465 Homo sapiens Pyroglutamyl-peptidase 1 Proteins 0.000 description 1
- 101000848724 Homo sapiens Rap guanine nucleotide exchange factor 3 Proteins 0.000 description 1
- 101001093899 Homo sapiens Retinoic acid receptor RXR-alpha Proteins 0.000 description 1
- 101000654301 Homo sapiens Secernin-3 Proteins 0.000 description 1
- 101000681218 Homo sapiens Transmembrane protein 215 Proteins 0.000 description 1
- 101000955093 Homo sapiens WD repeat-containing protein 3 Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102100033413 Protocadherin alpha-9 Human genes 0.000 description 1
- 102100031108 Pyroglutamyl-peptidase 1 Human genes 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 102100034584 Rap guanine nucleotide exchange factor 3 Human genes 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 102100035178 Retinoic acid receptor RXR-alpha Human genes 0.000 description 1
- 108010038912 Retinoid X Receptors Proteins 0.000 description 1
- 102000034527 Retinoid X Receptors Human genes 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 102100031320 Secernin-3 Human genes 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 201000000170 Thyroid lymphoma Diseases 0.000 description 1
- 101710170737 Transmembrane protein 215 Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 102100038964 WD repeat-containing protein 3 Human genes 0.000 description 1
- WCDYMMVGBZNUGB-ORPFKJIMSA-N [(2r,3r,4s,5r,6r)-6-[[(1r,3r,4r,5r,6r)-4,5-dihydroxy-2,7-dioxabicyclo[4.2.0]octan-3-yl]oxy]-3,4,5-trihydroxyoxan-2-yl]methyl 3-hydroxy-2-tetradecyloctadecanoate Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](COC(=O)C(CCCCCCCCCCCCCC)C(O)CCCCCCCCCCCCCCC)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H]2OC[C@H]2O1 WCDYMMVGBZNUGB-ORPFKJIMSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000036978 cell physiology Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 239000004030 hiv protease inhibitor Substances 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 208000025402 neoplasm of esophagus Diseases 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000032361 posttranscriptional gene silencing Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 208000024719 uterine cervix neoplasm Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61P31/10—Antimycotics
-
- 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
- A61P31/12—Antivirals
-
- 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
-
- 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
- C12N15/1137—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 enzymes
-
- 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
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
-
- 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
- C12N2310/18—Type of nucleic acid acting by a non-sequence specific mechanism
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
- C12N2310/3181—Peptide nucleic acid, PNA
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
Abstract
【選択図】図2
Description
生物学的有効分子を含み、更なる成分も含むことができる少なくとも1個のアンプル(アンプルA)と、
例えばナノ粒子、ポリエチレンイミン又は脂質のトランスフェクションシステムを有する少なくとも1個のアンプル(アンプルB)と、
前記生物学的有効分子に結合するための他の成分又はトランスフェクションシステムを含む少なくとも1個のアンプル(アンプルC)と、
アンプルA、B、Cの内容物のための希釈緩衝剤及び反応緩衝剤と、
1以上のカテーテル付き若しくはカニューレ付き注射器、及び標的細胞を含む媒体にアンプル内容物からなる混合物を注入するのに必要とされる他の器材と、
適用及び投与に関する指示書。
以下、図面を参照しつつ本発明の実施形態を詳述する。
2 細胞
3 遺伝子特異的なmRNA
4 遺伝子特異的なmRNA
5 遺伝子特異的なmRNA
6 遺伝子特異的なmRNA
7 分解された遺伝子特異的なmRNA
8 siRNA
9 分解された遺伝子特異的なmRNA
10 分解された遺伝子特異的なmRNA
11 分解された遺伝子特異的なmRNA
12 siRNA
Claims (13)
- 細胞に選択的に影響を及ぼすためにmRNAと結合するように調節された少なくとも1種の塩基配列を有する生物学的有効ヌクレオチド分子であって、ヌクレオチド分子(8)の少なくとも1種の塩基配列は複数の遺伝子のmRNA(3、4、5、6)と結合可能に設計されており、該ヌクレオチド分子が該遺伝子のmRNA(3、4、5、6)に結合することにより、細胞殺滅ストレス状態をもたらすために細胞(2)に有毒に作用する複数、特に多数の「オフターゲット」効果を誘起することを特徴とする、生物学的有効ヌクレオチド分子。
- ヌクレオチドとしてRNA、siRNA、PNA、DNA又はLNAが使用され、その大きさは10〜300bpであることを特徴とする、請求項1に記載の生物学的有効ヌクレオチド分子。
- 前記ヌクレオチド分子(8)は、mRNAに結合しなくともそれ自身で細胞内にストレス反応を誘起する特異的な塩基配列、例えばAAA、UUU、GCCA、UGGC、GUCCUUCAA、UGUGU、AUUUG、GUUUU、AUUUU、CUUUU、UUUUU又はGUUUGを含むことを特徴とする、請求項1又は2に記載の生物学的有効ヌクレオチド分子。
- 前記ヌクレオチド分子(8)は、特に細胞(2)内導入のために分子、例えば細胞貫通ペプチドと結合しており、或いは試薬、例えばポリエチレンイミン、ナノ粒子又は脂質に固定化されていることを特徴とする、請求項1〜3に記載の生物学的有効ヌクレオチド分子。
- 前記ヌクレオチド分子(8)は、塩基配列GGUA、CGUC、CGUU、CCAA、AAGG、GGUG、CUCG、CUCC、CUCU、CUUA、GGUC、GGUU、AAAG、AAAC、AAAU、AAGA、AAGC、AAGU、AACA、AACG、AACC、AACU、AAUA、CUUU,AAUG、AAUC、AAUU、AGGA、AGUG、AGUC、AGUU、ACAA、ACAG、ACAC、ACAU、ACGA、ACGG、ACGC、ACGU、ACCA、CAUU、CGAA、ACCG、ACCC、ACCU、ACUA、ACUG、ACUC、ACUU、AUAA、GGAG、GGAC、GGAU、GGGA、GGGC、GGGU、GGCA、GGCG、GGCC、GGCU、GCAA、GCAG、GCAC、GCAU、AUAG、AUAC、AUAU、AUGA、AUGG、AUGC、AUGU、AUCA、CGCG、CGCC、CGCU、AUCG、AUCC、AUCU、AUUA、AUUG、AUUC、AUUU、GAAA、GAAG、GAAC、GAAU、GAGA、GAGG、GAGC、GAGU、GACA、GACG、GACC、GACU、GAUA、GAUG、GAUC、GAUU、GGAA、GCGA、GCGG、GCGC、GCGU、GCCA、GCCG、GCCC、GCCU、GCUA、GCUG、GCUC、GCUU、GUAA、GUAG、GUAC、GUAU、GUGA、GUGG、GUGC、GUGU、GUCA、GUCG、GUCC、GUCU、GUUA、GUUG、GUUC、GUUU、CAAA、CAAG、CAAC、CAAU、CAGA、CAGG、CAGC、CAGU、CACA、CACG、CACC、CACU、CAUA、CAUG、CAUC、CGAG、CGAC、CGAU、CGGA、CGGG、CGGC、CGGU、CGCA、CGUA、CGUG、CCAG、CCAC、CCAU、CCGA、CCGG、CCGC、CCGU、CCCA、AGAA、AGAG、AGAC、AGAU、CCCG、CCCU、AGGG、AGGC、AGGU、AGCA,CCUA、CCUG、CCUC、CCUU、CUAA、CUAG、CUAC、CUAU、AGCG、AGUA、CUGA、CUGG、CUGC、CUGU、CUCA、CUUG、CUUC、AGCC及びAGCUの少なくとも1個を含むことを特徴とする、請求項1〜4の1項又は複数項に記載の生物学的有効ヌクレオチド分子。
- GUCUAUCAGCACAAUtt(配列番号:1)、GCUUAACUGUAUCUGGAGCtt(配列番号:2)、UUAACUGUAUCUGGAGCtt(配列番号:3)、AACUGUAUCUGGAGCtt(配列番号:4)、GCUCACCAAUGGAGAtt(配列番号:5)、GGCUGAACAAAGGAGAtt(配列番号:6)及びUGGCUGGCUGGCUGGCtt(配列番号:7)からなる群から選択される、請求項1又は2に記載の生物学的有効分子。
- 請求項1〜6のいずれか1項に記載の生物学的有効ヌクレオチド分子を含む医薬品。
- 腫瘍疾患又はウイルス誘発疾患の治療及び/又は予防に用いるための、請求項1〜6のいずれか1項に記載の生物学的有効ヌクレオチド分子。
- 真核細胞、特に動物細胞、植物細胞又は真菌細胞を選択的に殺滅するための、請求項1〜6に記載の生物学的有効ヌクレオチド分子の使用。
- ウイルス感染細胞を選択的に殺滅するための、請求項1〜6に記載の生物学的有効ヌクレオチド分子の使用。
- 原核細胞を選択的に殺滅するための、請求項1〜6に記載の生物学的有効ヌクレオチド分子の使用。
- プロテアーゼ阻害剤と組み合わせて用いることを特徴とする、請求項1〜6に記載の生物学的有効ヌクレオチド分子の使用。
- 請求項1〜5に記載の生物学的有効ヌクレオチド分子を適用及び投与するための適用キットであって、
生物学的有効分子を含み、更なる成分も含むことができる少なくとも1個のアンプル(アンプルA)と、
例えば細胞貫通ペプチド、ナノ粒子、ポリエチレンイミン又は脂質のトランスフェクションシステムを有する少なくとも1個のアンプル(アンプルB)と、
前記生物学的有効分子に結合するための他の成分又はトランスフェクションシステムを含む少なくとも1個のアンプル(アンプルC)と、
アンプルA、Bの内容物のための希釈緩衝剤及び反応緩衝剤と、
1以上のカテーテル付き若しくはカニューレ付き注射器、及び標的細胞を含む媒体にアンプル内容物からなる混合物を注入するのに必要とされる他の器材と、
適用及び投与に関する指示書とを少なくとも含むキット。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102011009470A DE102011009470A1 (de) | 2011-01-21 | 2011-01-21 | Biologisch wirksame Nukleotid-Moleküle zur gezielten Abtötung von Zellen, Verwendung derselben sowie Applikationskit |
DE102011009470.9 | 2011-01-21 | ||
PCT/EP2012/050879 WO2012098234A1 (de) | 2011-01-21 | 2012-01-20 | Biologisch wirksame nukleotid-moleküle zur gezielten abtötung von zellen, verwendung derselben sowie applikationskit |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2014511173A true JP2014511173A (ja) | 2014-05-15 |
Family
ID=45688436
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013549831A Pending JP2014511173A (ja) | 2011-01-21 | 2012-01-20 | 選択的細胞殺滅のための生物学的有効ヌクレオチド分子、その使用及び適用キット |
Country Status (6)
Country | Link |
---|---|
US (1) | US20170233760A1 (ja) |
EP (1) | EP2665816A1 (ja) |
JP (1) | JP2014511173A (ja) |
CN (1) | CN103597075A (ja) |
DE (1) | DE102011009470A1 (ja) |
WO (1) | WO2012098234A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102013003869B4 (de) | 2013-02-27 | 2016-11-24 | Friedrich-Schiller-Universität Jena | Verfahren zur gezielten Abtötung von Zellen durch zur mRNA-Anbindung ausgerichtete Nukleotid-Moleküle sowie Nukleotid-Moleküle und Applikationskit für solche Verwendung |
MA53381A (fr) | 2018-07-24 | 2021-06-02 | Amgen Inc | Association d'inhibiteurs de la voie lilrb1/2 et d'inhibiteurs de la voie pd-1 |
DE102019000490A1 (de) | 2019-01-23 | 2020-07-23 | HAEMES Verwaltungsgesellschaft mbH | Verwendung von Oligonukleotiden für die Behandlung von Tumoren |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004048511A2 (en) * | 2002-11-26 | 2004-06-10 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel viral regulatory genes and uses thereof |
KR20070114923A (ko) * | 2006-05-30 | 2007-12-05 | 울산대학교 산학협력단 | 복수의 표적 mRNA에 적용 가능한 siRNA염기서열을 추출하는 방법 |
WO2009083790A2 (en) * | 2007-12-28 | 2009-07-09 | Qiagen Sciences, Inc | 'apoptosis inducing positive control for expression modulating experiments' |
JP2010538660A (ja) * | 2007-09-17 | 2010-12-16 | イントラドイグム コーポレーション | STAT3siRNA含有組成物及びそれらの使用法 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
TR200401292T3 (tr) | 2000-12-01 | 2004-07-21 | Max@Planck@Gesellschaft�Zur�F�Rderung�Der�Wissenschaften | RNAÁgirişimineÁyolÁaçanÁküçükÁRNAÁmolekülleri |
EP1628993A4 (en) * | 2003-05-16 | 2010-04-07 | Rosetta Inpharmatics Llc | METHOD AND COMPOSITIONS FOR RNA INTERFERENCE |
US7858769B2 (en) * | 2004-02-10 | 2010-12-28 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using multifunctional short interfering nucleic acid (multifunctional siNA) |
US7404969B2 (en) * | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
US8071752B2 (en) * | 2007-01-29 | 2011-12-06 | City Of Hope | Multi-targeting short interfering RNAs |
DE102007008596B4 (de) | 2007-02-15 | 2010-09-02 | Friedrich-Schiller-Universität Jena | Biologisch wirksame Moleküle auf Grundlage von PNA und siRNA, Verfahren zu deren zellspezifischen Aktivierung sowie Applikationskit zur Verabreichung |
WO2009020344A2 (en) * | 2007-08-06 | 2009-02-12 | Postech Acad Ind Found | Small interfering rnas (sirnas) controlling multiple target genes and method for preparing the same |
DE102009043743B4 (de) * | 2009-03-13 | 2016-10-13 | Friedrich-Schiller-Universität Jena | Zellspezifisch wirksame Moleküle auf Grundlage von siRNA sowie Applikationskits zu deren Herstellung und Verwendung |
GB2468477A (en) * | 2009-03-02 | 2010-09-15 | Mina Therapeutics Ltd | Double stranded RNA molecule comprising siRNA and miRNA precursors |
-
2011
- 2011-01-21 DE DE102011009470A patent/DE102011009470A1/de not_active Withdrawn
-
2012
- 2012-01-20 EP EP12704718.1A patent/EP2665816A1/de not_active Withdrawn
- 2012-01-20 US US13/979,084 patent/US20170233760A1/en not_active Abandoned
- 2012-01-20 WO PCT/EP2012/050879 patent/WO2012098234A1/de active Application Filing
- 2012-01-20 JP JP2013549831A patent/JP2014511173A/ja active Pending
- 2012-01-20 CN CN201280006049.7A patent/CN103597075A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004048511A2 (en) * | 2002-11-26 | 2004-06-10 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel viral regulatory genes and uses thereof |
KR20070114923A (ko) * | 2006-05-30 | 2007-12-05 | 울산대학교 산학협력단 | 복수의 표적 mRNA에 적용 가능한 siRNA염기서열을 추출하는 방법 |
JP2010538660A (ja) * | 2007-09-17 | 2010-12-16 | イントラドイグム コーポレーション | STAT3siRNA含有組成物及びそれらの使用法 |
WO2009083790A2 (en) * | 2007-12-28 | 2009-07-09 | Qiagen Sciences, Inc | 'apoptosis inducing positive control for expression modulating experiments' |
Non-Patent Citations (2)
Title |
---|
JPN6015006900; RNA vol.12, 2006, p.1188-96 * |
JPN6015006902; Pathol. Oncol. Res. vol.13, 2007, p.84-90 * |
Also Published As
Publication number | Publication date |
---|---|
EP2665816A1 (de) | 2013-11-27 |
US20170233760A1 (en) | 2017-08-17 |
CN103597075A (zh) | 2014-02-19 |
WO2012098234A1 (de) | 2012-07-26 |
DE102011009470A1 (de) | 2012-08-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2489167C2 (ru) | Модифицированная липидом двухцепочечная рнк, обладающая эффектом рнк-интерференции | |
US11091761B2 (en) | Organic compositions to treat HSF1-related diseases | |
EP2264167B1 (en) | Double-stranded lipid-modified rna having high rna interference effect | |
AU2020200247A1 (en) | Organic compositions to treat KRAS-related diseases | |
US20100069620A1 (en) | Novel compositions of chemically modified small interfering rna | |
AU2014306416A9 (en) | Compositions and methods for modulating RNA | |
JP2015518712A (ja) | Mecp2発現を調節するための組成物及び方法 | |
JP2006520760A (ja) | 短鎖干渉RNA(siRNA)アナログ | |
JP2016521556A (ja) | Foxp3発現を調節するための組成物及び方法 | |
JP2016531570A (ja) | ユークロマチン領域を標的とするオリゴヌクレオチド | |
KR101142080B1 (ko) | 전립선암 및 다른 암의 치료 방법 및 조성물 | |
TW201726920A (zh) | 具高活性及減低脫靶之siRNA構造 | |
JP2014511173A (ja) | 選択的細胞殺滅のための生物学的有効ヌクレオチド分子、その使用及び適用キット | |
CN111154755B (zh) | 一种双链寡核苷酸dna及其应用 | |
EP3180033B1 (de) | Peptid zur verwendung in der reduktion von nebenwirkungen in form von immunstimulatorischen reaktionen/effekten | |
Ruppa et al. | CMC and regulatory aspects therapeutics☆ of oligonucleotide | |
Gewirtz | Nucleic Acid-Based, mRNA-Targeted Therapeutics for Hematologic Malignancies | |
Delihas | Targeting the expression of anti-apoptotic proteins by antisense oligonucleotides | |
WO2007087544A2 (en) | Novel compositions of chemically modified small interfering rna |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150224 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150521 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150623 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150723 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150821 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20150821 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160105 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160330 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20160330 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160524 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20161220 |