CN107236735B - 包含锁核酸基序的基于寡核苷酸的抑制剂 - Google Patents
包含锁核酸基序的基于寡核苷酸的抑制剂 Download PDFInfo
- Publication number
- CN107236735B CN107236735B CN201710249089.9A CN201710249089A CN107236735B CN 107236735 B CN107236735 B CN 107236735B CN 201710249089 A CN201710249089 A CN 201710249089A CN 107236735 B CN107236735 B CN 107236735B
- Authority
- CN
- China
- Prior art keywords
- mod
- res
- phosphorothioate
- nucleic acid
- mir
- 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.)
- Expired - Fee Related
Links
- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 255
- 150000007523 nucleic acids Chemical group 0.000 title abstract description 10
- 239000003112 inhibitor Substances 0.000 title description 32
- 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 abstract description 125
- 239000003814 drug Substances 0.000 claims abstract description 12
- -1 microballoon Substances 0.000 claims description 402
- 210000004027 cell Anatomy 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 108091034121 miR-92a stem-loop Proteins 0.000 claims description 10
- 108091041519 miR-92a-3 stem-loop Proteins 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 8
- 238000000338 in vitro Methods 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000006185 dispersion Substances 0.000 claims description 6
- 239000000693 micelle Substances 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000002502 liposome Substances 0.000 claims description 5
- 210000002064 heart cell Anatomy 0.000 claims description 4
- 239000002105 nanoparticle Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 210000004962 mammalian cell Anatomy 0.000 claims description 3
- 239000002088 nanocapsule Substances 0.000 claims description 3
- 239000000084 colloidal system Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000007764 o/w emulsion Substances 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 abstract description 384
- 108020004707 nucleic acids Proteins 0.000 abstract description 384
- 108091070501 miRNA Proteins 0.000 abstract description 123
- 239000002679 microRNA Substances 0.000 abstract description 121
- 108091032973 (ribonucleotides)n+m Proteins 0.000 abstract description 97
- 238000001727 in vivo Methods 0.000 abstract description 42
- 239000000203 mixture Substances 0.000 abstract description 30
- 238000007385 chemical modification Methods 0.000 abstract description 17
- 108020004999 messenger RNA Proteins 0.000 abstract description 17
- 238000000034 method Methods 0.000 abstract description 17
- 230000008685 targeting Effects 0.000 abstract description 15
- 239000000074 antisense oligonucleotide Substances 0.000 abstract description 7
- 238000012230 antisense oligonucleotides Methods 0.000 abstract description 7
- 108020000948 Antisense Oligonucleotides Proteins 0.000 abstract description 6
- 231100000419 toxicity Toxicity 0.000 abstract description 6
- 230000001988 toxicity Effects 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 229940124597 therapeutic agent Drugs 0.000 abstract description 4
- 230000008901 benefit Effects 0.000 abstract description 3
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 386
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 261
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 258
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 258
- 229940104230 thymidine Drugs 0.000 description 258
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 240
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 196
- 229940104302 cytosine Drugs 0.000 description 182
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 130
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 130
- 229940029575 guanosine Drugs 0.000 description 130
- 108020004414 DNA Proteins 0.000 description 79
- 241000282414 Homo sapiens Species 0.000 description 79
- 125000003729 nucleotide group Chemical group 0.000 description 70
- 239000002773 nucleotide Substances 0.000 description 68
- UBCPYVAQZGCDJO-KQYNXXCUSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(dihydroxyphosphinothioyloxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=S)[C@@H](O)[C@H]1O UBCPYVAQZGCDJO-KQYNXXCUSA-N 0.000 description 45
- 210000002216 heart Anatomy 0.000 description 33
- 108091071651 miR-208 stem-loop Proteins 0.000 description 31
- 108091084446 miR-208a stem-loop Proteins 0.000 description 31
- 108091062547 miR-208a-1 stem-loop Proteins 0.000 description 31
- 108091055375 miR-208a-2 stem-loop Proteins 0.000 description 31
- 230000000295 complement effect Effects 0.000 description 28
- 150000001875 compounds Chemical class 0.000 description 28
- 230000004048 modification Effects 0.000 description 27
- 238000012986 modification Methods 0.000 description 27
- 230000005764 inhibitory process Effects 0.000 description 26
- 230000000694 effects Effects 0.000 description 24
- 239000002585 base Substances 0.000 description 23
- 108091047268 miR-208b stem-loop Proteins 0.000 description 23
- 210000004185 liver Anatomy 0.000 description 22
- 210000001519 tissue Anatomy 0.000 description 22
- OIRDTQYFTABQOQ-KQYNXXCUSA-N Adenosine Natural products C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 20
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 20
- 229960005305 adenosine Drugs 0.000 description 20
- 210000005003 heart tissue Anatomy 0.000 description 19
- 241000700159 Rattus Species 0.000 description 18
- 108091027983 miR-378-1 stem-loop Proteins 0.000 description 18
- 108091089716 miR-378-2 stem-loop Proteins 0.000 description 18
- 238000003753 real-time PCR Methods 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 238000002347 injection Methods 0.000 description 16
- 239000007924 injection Substances 0.000 description 16
- 238000009826 distribution Methods 0.000 description 15
- 210000003734 kidney Anatomy 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 15
- 108091056170 miR-499 stem-loop Proteins 0.000 description 14
- 108091050885 miR-499-1 stem-loop Proteins 0.000 description 14
- 108091038523 miR-499-2 stem-loop Proteins 0.000 description 14
- 108091007431 miR-29 Proteins 0.000 description 13
- 238000009472 formulation Methods 0.000 description 12
- 108091028049 Mir-221 microRNA Proteins 0.000 description 10
- 125000001921 locked nucleotide group Chemical group 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 208000035657 Abasia Diseases 0.000 description 9
- 108091025686 miR-199a stem-loop Proteins 0.000 description 9
- 108091033319 polynucleotide Proteins 0.000 description 9
- 239000002157 polynucleotide Substances 0.000 description 9
- 102000040430 polynucleotide Human genes 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 description 9
- 230000000747 cardiac effect Effects 0.000 description 7
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 7
- CGPPXVAUDMUIPK-UHFFFAOYSA-N phosphoric acid trihydroxy(sulfanylidene)-lambda5-phosphane Chemical class OP(O)(O)=O.OP(O)(O)=S CGPPXVAUDMUIPK-UHFFFAOYSA-N 0.000 description 7
- 238000012453 sprague-dawley rat model Methods 0.000 description 7
- 101150113075 DYNLT1 gene Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000000692 anti-sense effect Effects 0.000 description 6
- 238000007479 molecular analysis Methods 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 5
- 208000006029 Cardiomegaly Diseases 0.000 description 5
- 206010013142 Disinhibition Diseases 0.000 description 5
- 206010019280 Heart failures Diseases 0.000 description 5
- 108091007775 MIR1-1 Proteins 0.000 description 5
- 108091026807 MiR-214 Proteins 0.000 description 5
- 108091081013 MiR-33 Proteins 0.000 description 5
- 108091028066 Mir-126 Proteins 0.000 description 5
- 108091060568 Mir-133 microRNA precursor family Proteins 0.000 description 5
- 108091027766 Mir-143 Proteins 0.000 description 5
- 108091028684 Mir-145 Proteins 0.000 description 5
- 108091060302 Mir-320 Proteins 0.000 description 5
- 101710163270 Nuclease Proteins 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 230000009977 dual effect Effects 0.000 description 5
- 210000002889 endothelial cell Anatomy 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000007918 intramuscular administration Methods 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 108091053410 let-7 family Proteins 0.000 description 5
- 210000005228 liver tissue Anatomy 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 108091028606 miR-1 stem-loop Proteins 0.000 description 5
- 108091044592 miR-1-1 stem-loop Proteins 0.000 description 5
- 108091045542 miR-1-2 stem-loop Proteins 0.000 description 5
- 108091091360 miR-125b stem-loop Proteins 0.000 description 5
- 108091023685 miR-133 stem-loop Proteins 0.000 description 5
- 108091031326 miR-15b stem-loop Proteins 0.000 description 5
- 108091027943 miR-16 stem-loop Proteins 0.000 description 5
- 108091074057 miR-16-1 stem-loop Proteins 0.000 description 5
- 108091056204 miR-16-2 stem-loop Proteins 0.000 description 5
- 108091062762 miR-21 stem-loop Proteins 0.000 description 5
- 108091041631 miR-21-1 stem-loop Proteins 0.000 description 5
- 108091044442 miR-21-2 stem-loop Proteins 0.000 description 5
- 108091061917 miR-221 stem-loop Proteins 0.000 description 5
- 108091063489 miR-221-1 stem-loop Proteins 0.000 description 5
- 108091055391 miR-221-2 stem-loop Proteins 0.000 description 5
- 108091031076 miR-221-3 stem-loop Proteins 0.000 description 5
- 108091080321 miR-222 stem-loop Proteins 0.000 description 5
- 108091092825 miR-24 stem-loop Proteins 0.000 description 5
- 108091032978 miR-24-3 stem-loop Proteins 0.000 description 5
- 108091064025 miR-24-4 stem-loop Proteins 0.000 description 5
- 108091085564 miR-25 stem-loop Proteins 0.000 description 5
- 108091080167 miR-25-1 stem-loop Proteins 0.000 description 5
- 108091083056 miR-25-2 stem-loop Proteins 0.000 description 5
- 108091061970 miR-26a stem-loop Proteins 0.000 description 5
- 108091029119 miR-34a stem-loop Proteins 0.000 description 5
- 108091079013 miR-34b Proteins 0.000 description 5
- 108091084018 miR-34b stem-loop Proteins 0.000 description 5
- 108091063470 miR-34b-1 stem-loop Proteins 0.000 description 5
- 108091049916 miR-34b-2 stem-loop Proteins 0.000 description 5
- 108091057222 miR-34b-3 stem-loop Proteins 0.000 description 5
- 108091092639 miR-34b-4 stem-loop Proteins 0.000 description 5
- 108091090583 miR-34c stem-loop Proteins 0.000 description 5
- 108091082133 miR-34c-1 stem-loop Proteins 0.000 description 5
- 108091030938 miR-424 stem-loop Proteins 0.000 description 5
- 108091052738 miR-486-1 stem-loop Proteins 0.000 description 5
- 108091030654 miR-486-2 stem-loop Proteins 0.000 description 5
- 108091063340 miR-497 stem-loop Proteins 0.000 description 5
- 108091059456 miR-92-1 stem-loop Proteins 0.000 description 5
- 108091084336 miR-92-2 stem-loop Proteins 0.000 description 5
- 238000010172 mouse model Methods 0.000 description 5
- 231100000417 nephrotoxicity Toxicity 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 125000001475 halogen functional group Chemical group 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000002719 pyrimidine nucleotide Substances 0.000 description 4
- 150000003230 pyrimidines Chemical class 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 238000011552 rat model Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 210000005084 renal tissue Anatomy 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 102100024810 DNA (cytosine-5)-methyltransferase 3B Human genes 0.000 description 3
- 101710123222 DNA (cytosine-5)-methyltransferase 3B Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 101150042096 Gfpt2 gene Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 231100000304 hepatotoxicity Toxicity 0.000 description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 210000005240 left ventricle Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 150000008300 phosphoramidites Chemical class 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002213 purine nucleotide Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 231100000440 toxicity profile Toxicity 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 101150118748 Ddr1 gene Proteins 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000001246 colloidal dispersion Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 101150094281 mcl1 gene Proteins 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 230000004001 molecular interaction Effects 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 108091007428 primary miRNA Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 239000002510 pyrogen Substances 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000005451 thionucleotide Substances 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108020004394 Complementary RNA Proteins 0.000 description 1
- 208000002330 Congenital Heart Defects Diseases 0.000 description 1
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 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 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 108091092539 MiR-208 Proteins 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 206010029155 Nephropathy toxic Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- SKWPGOJVPWRYQJ-UHFFFAOYSA-N OP(O)(O)=O.OP(O)(S)=S Chemical compound OP(O)(O)=O.OP(O)(S)=S SKWPGOJVPWRYQJ-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000031964 Other metabolic disease Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 206010063897 Renal ischaemia Diseases 0.000 description 1
- 241000242739 Renilla Species 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000242583 Scyphozoa Species 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000000799 fusogenic effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002960 lipid emulsion Substances 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical group CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 108091035155 miR-10a stem-loop Proteins 0.000 description 1
- 108091007432 miR-29b Proteins 0.000 description 1
- 108091007426 microRNA precursor Proteins 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 229940064696 nutrilipid Drugs 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 208000030613 peripheral artery disease Diseases 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000011191 terminal modification Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
- C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- 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
- C12N2310/317—Chemical structure of the backbone with an inverted bond, e.g. a cap structure
-
- 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
-
- 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
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/345—Spatial arrangement of the modifications having at least two different backbone modifications
-
- 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
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261662746P | 2012-06-21 | 2012-06-21 | |
| US61/662,746 | 2012-06-21 | ||
| US201361801533P | 2013-03-15 | 2013-03-15 | |
| US61/801,533 | 2013-03-15 | ||
| CN201380038840.0A CN104685056A (zh) | 2012-06-21 | 2013-06-21 | 包含锁核酸基序的基于寡核苷酸的抑制剂 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380038840.0A Division CN104685056A (zh) | 2012-06-21 | 2013-06-21 | 包含锁核酸基序的基于寡核苷酸的抑制剂 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107236735A CN107236735A (zh) | 2017-10-10 |
| CN107236735B true CN107236735B (zh) | 2019-11-08 |
Family
ID=49769732
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710249089.9A Expired - Fee Related CN107236735B (zh) | 2012-06-21 | 2013-06-21 | 包含锁核酸基序的基于寡核苷酸的抑制剂 |
| CN201380038840.0A Pending CN104685056A (zh) | 2012-06-21 | 2013-06-21 | 包含锁核酸基序的基于寡核苷酸的抑制剂 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380038840.0A Pending CN104685056A (zh) | 2012-06-21 | 2013-06-21 | 包含锁核酸基序的基于寡核苷酸的抑制剂 |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US9388408B2 (enExample) |
| EP (2) | EP2864482A4 (enExample) |
| JP (2) | JP6208228B2 (enExample) |
| KR (1) | KR101928418B1 (enExample) |
| CN (2) | CN107236735B (enExample) |
| AU (1) | AU2013278011B2 (enExample) |
| CA (1) | CA2876180C (enExample) |
| DK (1) | DK3354734T3 (enExample) |
| ES (1) | ES2801875T3 (enExample) |
| HK (2) | HK1209781A1 (enExample) |
| MX (1) | MX355408B (enExample) |
| WO (1) | WO2013192576A2 (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8642751B2 (en) * | 2010-12-15 | 2014-02-04 | Miragen Therapeutics | MicroRNA inhibitors comprising locked nucleotides |
| EP2702155B9 (en) | 2011-04-25 | 2020-01-01 | Regulus Therapeutics Inc. | Microrna compounds and methods for modulating mir-21 activity |
| PH12023550488A1 (en) | 2012-04-25 | 2024-06-24 | Sanofi Sa | Microrna compounds and methods for modulating mir-21 activity |
| JP6208228B2 (ja) | 2012-06-21 | 2017-10-04 | ミラゲン セラピューティクス， インコーポレイテッド | ロックド核酸モチーフを含むオリゴヌクレオチドベースの阻害剤 |
| UA116639C2 (uk) | 2012-10-09 | 2018-04-25 | Рег'Юлес Терап'Ютікс Інк. | Способи лікування синдрому альпорта |
| EP2757157A1 (en) * | 2013-01-17 | 2014-07-23 | Ecole Polytechnique Federale de Lausanne (EPFL) | Modulation of mitophagy and use thereof |
| US9752143B2 (en) | 2013-03-15 | 2017-09-05 | MiRagen Therapeutics, Inc. | Locked nucleic acid inhibitor of miR-145 and uses thereof |
| TW201446791A (zh) | 2013-05-01 | 2014-12-16 | Regulus Therapeutics Inc | 用於調節mir-122之微小rna化合物及方法 |
| AU2015301221B2 (en) | 2014-08-04 | 2020-07-02 | MiRagen Therapeutics, Inc. | Inhibitors of MYH7B and uses thereof |
| RU2017105342A (ru) | 2014-08-07 | 2018-09-13 | Регулус Терапьютикс Инк. | НАЦЕЛИВАНИЕ НА микроРНК ПРИ РАССТРОЙСТВАХ ОБМЕНА ВЕЩЕСТВ |
| WO2016069717A1 (en) * | 2014-10-28 | 2016-05-06 | MiRagen Therapeutics, Inc. | Inhibitors of mirnas in regulation of arterial stiffness and uses thereof |
| EP3247716A4 (en) * | 2015-01-20 | 2018-10-17 | Miragen Therapeutics, Inc. | Mir-92 inhibitors and uses thereof |
| US10538769B2 (en) | 2015-09-04 | 2020-01-21 | Oregon State University | Renal selective inhibition of cytochrome P450 3A5 |
| WO2017053622A1 (en) * | 2015-09-22 | 2017-03-30 | MiRagen Therapeutics, Inc. | MiR-19 MODULATORS AND USES THEREOF |
| EP3985116A1 (en) * | 2015-10-15 | 2022-04-20 | City of Hope | Compounds and compositions including phosphorothioated oligodeoxynucleotide, and methods of use thereof |
| US10357543B2 (en) | 2015-11-16 | 2019-07-23 | Ohio State Innovation Foundation | Methods and compositions for treating disorders and diseases using Survival Motor Neuron (SMN) protein |
| CN105435247A (zh) * | 2015-12-31 | 2016-03-30 | 中国医学科学院基础医学研究所 | miR-378在预防和/或治疗肥胖症中的用途 |
| EP3449001B1 (en) * | 2016-04-29 | 2021-12-08 | Aptamir Therapeutics, Inc. | Inhibition of mir-22 mirna by apt-110 |
| CN106011140B (zh) * | 2016-06-06 | 2018-12-18 | 同济大学 | 反义microRNA-25及其应用 |
| WO2017214952A1 (zh) * | 2016-06-16 | 2017-12-21 | 毛侃琅 | 特异抑制人 miRNA-185 表达的慢病毒载体的构建及其应用 |
| WO2017214953A1 (zh) * | 2016-06-16 | 2017-12-21 | 毛侃琅 | 一种特异抑制人 miRNA-424 表达的慢病毒载体的构建及其应用 |
| WO2017219170A1 (zh) * | 2016-06-19 | 2017-12-28 | 毛侃琅 | 特异抑制人 miRNA-29a 和 miR-424 表达的慢病毒载体的构建及其应用 |
| WO2017219166A1 (zh) * | 2016-06-19 | 2017-12-28 | 毛侃琅 | 一种同时抑制双 miRNA 表达的慢病毒载体及其应用 |
| WO2017219165A1 (zh) * | 2016-06-19 | 2017-12-28 | 毛侃琅 | 特异敲低人 miRNA-29a 和 miR-140 表达的慢病毒载体及其应用 |
| US20200276220A1 (en) * | 2016-07-07 | 2020-09-03 | MiRagen Therapeutics, Inc. | Methods for treating cutaneous t-cell lymphoma (ctcl) with mir-155 inhibitors |
| JP7303107B2 (ja) | 2016-08-12 | 2023-07-04 | イムノワーク，リミテッド ライアビリティ カンパニー | 自己免疫疾患の診断、予防、および／または治療 |
| AU2017368050A1 (en) | 2016-11-29 | 2019-06-20 | Puretech Lyt, Inc. | Exosomes for delivery of therapeutic agents |
| WO2018183127A1 (en) * | 2017-03-25 | 2018-10-04 | MiRagen Therapeutics, Inc. | Mir-92 inhibitors for treatment of heart failure |
| CN110141577A (zh) * | 2018-02-13 | 2019-08-20 | 上海三炬生物科技有限公司 | miRNA-24-3p核苷酸类似物在制备药物中的应用 |
| JP7318166B2 (ja) * | 2018-03-14 | 2023-08-01 | ベス イスラエル デアコネス メディカル センター | マイクロｒｎａ２２の阻害剤 |
| CN112400020B (zh) | 2018-05-08 | 2024-11-19 | 莱古路斯治疗法股份有限公司 | 作为具有hcv抗病毒活性与降低的高胆红素血症副作用的mir-122抑制剂的galnac缀合的经修饰的寡核苷酸 |
| US20220056443A1 (en) * | 2018-09-06 | 2022-02-24 | Aptamir Therapeutics, Inc. | Metabolic benefits of short mir-22 mirna antagomir therapies |
| CN110358769A (zh) * | 2019-07-30 | 2019-10-22 | 中国医学科学院血液病医院(中国医学科学院血液学研究所) | 经锁核酸和硫代磷酸修饰的miRNA类似物及其在制备抗肿瘤药物中的应用 |
| CN110433170B (zh) * | 2019-07-31 | 2021-04-27 | 南京医科大学 | 心脏抽吸液miR-28-5p在心脏疾病中的应用 |
| IT201900017234A1 (it) * | 2019-09-25 | 2021-03-25 | Int Centre For Genetic Engineering And Biotechnology | Anti-miRNA per il trattamento del leiomioma |
| WO2021097390A1 (en) * | 2019-11-15 | 2021-05-20 | Duke University | Cellular molecular theranostics nanoprobe systems and methods |
| CN111118008B (zh) * | 2020-01-16 | 2023-08-22 | 南京医科大学 | Mcl1基因的3’-UTR序列及其应用 |
| EP4114938A4 (en) * | 2020-03-04 | 2025-02-19 | The Trustees of Indiana University | Methods to re-engage a fetal wound healing pathway for adult skin repair |
| JP2023538496A (ja) * | 2020-07-23 | 2023-09-08 | ヨハン ヴォルフガング ゲーテ－ウニヴェルズィテート フランクフルト | 心不全治療のためのｍｉＲＮＡのコンビナトリアル阻害 |
| JP2024504679A (ja) * | 2021-01-18 | 2024-02-01 | リジェン イノファーム インコーポレイテッド | ｍｉＲ１４５阻害剤を有効成分として含む心筋梗塞の治療用組成物 |
| WO2024165603A1 (en) | 2023-02-07 | 2024-08-15 | Universitetet I Tromsø - Norges Arktiske Universitet | Pharmaceutical composition for use in treatment of venous thromboembolism |
| GB202305535D0 (en) | 2023-04-14 | 2023-05-31 | Imperial College Innovations Ltd | Oligonucleotide decoy |
| WO2025008641A2 (en) * | 2023-07-06 | 2025-01-09 | Imperial College Innovations Limited | Rna molecule |
| WO2025104709A1 (en) * | 2023-11-17 | 2025-05-22 | Biorchestra Co., Ltd. | Microrna-378a-3p antisense oligonucleotides and uses thereof |
Family Cites Families (112)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5981505A (en) | 1993-01-26 | 1999-11-09 | The Trustees Of The University Of Pennsylvania | Compositions and methods for delivery of genetic material |
| WO1995003843A1 (en) | 1993-07-30 | 1995-02-09 | The Regents Of The University Of California | Endocardial infusion catheter |
| US5837533A (en) | 1994-09-28 | 1998-11-17 | American Home Products Corporation | Complexes comprising a nucleic acid bound to a cationic polyamine having an endosome disruption agent |
| US5840710A (en) | 1994-12-09 | 1998-11-24 | Genzyme Corporation | Cationic amphiphiles containing ester or ether-linked lipophilic groups for intracellular delivery of therapeutic molecules |
| US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| US6416510B1 (en) | 1997-03-13 | 2002-07-09 | Biocardia, Inc. | Drug delivery catheters that attach to tissue and methods for their use |
| US6217900B1 (en) | 1997-04-30 | 2001-04-17 | American Home Products Corporation | Vesicular complexes and methods of making and using the same |
| ATE321882T1 (de) | 1997-07-01 | 2006-04-15 | Isis Pharmaceuticals Inc | Zusammensetzungen und verfahren zur verabreichung von oligonukleotiden über die speiseröhre |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| US6749617B1 (en) | 1997-11-04 | 2004-06-15 | Scimed Life Systems, Inc. | Catheter and implants for the delivery of therapeutic agents to tissues |
| SI20474A (sl) | 1998-05-26 | 2001-08-31 | Icn Pharmaceuticals, Inc. | Novi nukleozidi, ki imajo bicikličen sladkorni del |
| US6833361B2 (en) | 1998-05-26 | 2004-12-21 | Ribapharm, Inc. | Nucleosides having bicyclic sugar moiety |
| HK1048339A1 (zh) | 1999-03-18 | 2003-03-28 | 埃克西库恩公司 | 利用特异性lna引物检测基因突变 |
| WO2001025478A1 (en) * | 1999-10-04 | 2001-04-12 | Exiqon A/S | A method of increasing the specificity of oxy-lna oligonucleotides |
| DK1334109T3 (da) | 2000-10-04 | 2006-10-09 | Santaris Pharma As | Forbedret syntese af purin-blokerede nukleinsyre-analoger |
| EP2390328A1 (en) | 2001-09-28 | 2011-11-30 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | MicroRNA molecules |
| AU2003266014B2 (en) | 2002-05-06 | 2009-05-14 | Alnylam Pharmaceuticals, Inc. | Methods for delivery of nucleic acids |
| US20080214437A1 (en) | 2002-09-06 | 2008-09-04 | Mohapatra Shyam S | Methods and compositions for reducing activity of the atrial natriuretic peptide receptor and for treatment of diseases |
| DK2752488T3 (da) | 2002-11-18 | 2020-04-20 | Roche Innovation Ct Copenhagen As | Antisense-design |
| ES2576677T3 (es) | 2003-03-21 | 2016-07-08 | Roche Innovation Center Copenhagen A/S | Análogos de ARN interfirientes cortos |
| EP1648914A4 (en) | 2003-07-31 | 2009-12-16 | Regulus Therapeutics Inc | OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA |
| WO2005017145A1 (ja) | 2003-08-13 | 2005-02-24 | Japan Biological Informatics Consortium | 機能性ｒｎａが制御する被制御遺伝子の同定・予測方法及びその利用方法 |
| JP5654722B2 (ja) | 2003-11-26 | 2015-01-14 | ユニバーシティ オブ マサチューセッツ | 短鎖ｒｎａ機能の配列特異的阻害法 |
| CA2554818A1 (en) | 2004-02-09 | 2005-08-25 | Thomas Jefferson University | Diagnosis and treatment of cancers with microrna located in or near cancer-associated chromosomal features |
| US20050256072A1 (en) | 2004-02-09 | 2005-11-17 | University Of Massachusetts | Dual functional oligonucleotides for use in repressing mutant gene expression |
| CA2556435C (en) | 2004-02-13 | 2014-08-12 | The Rockefeller University | Anti-microrna oligonucleotide molecules |
| US7722596B2 (en) | 2004-02-26 | 2010-05-25 | Osprey Medical, Inc. | Regional cardiac tissue treatment |
| BRPI0508073A (pt) | 2004-02-26 | 2007-07-17 | Kardia Pty Ltd V | método e aparelho para isolar substancialmente circulação cardìaca da circulação sistêmica aparelho para perfundir o coração com um agente terapêutico, cateter de obstrução para obstruir fluxo entre um vaso principal e um ou mais vasos ramificados, método para administrar um agente terapêutico ao coração e estrutura de suporte percutaneamente administrável para manter patência do sinus coronário |
| US20070203445A1 (en) | 2004-02-26 | 2007-08-30 | V-Kardia Pty Ltd | Isolating cardiac circulation |
| EP2290071B1 (en) | 2004-05-28 | 2014-12-31 | Asuragen, Inc. | Methods and compositions involving microRNA |
| EP2314688B1 (en) | 2004-11-12 | 2014-07-16 | Asuragen, Inc. | Methods and compositions involving miRNA and miRNA inhibitor molecules |
| US9550990B2 (en) | 2004-12-10 | 2017-01-24 | Ionis Pharmaceuticals, Inc. | Regulation of epigenetic control of gene expression |
| US20060185027A1 (en) | 2004-12-23 | 2006-08-17 | David Bartel | Systems and methods for identifying miRNA targets and for altering miRNA and target expression |
| US20070099196A1 (en) | 2004-12-29 | 2007-05-03 | Sakari Kauppinen | Novel oligonucleotide compositions and probe sequences useful for detection and analysis of micrornas and their target mRNAs |
| US8071306B2 (en) | 2005-01-25 | 2011-12-06 | Merck Sharp & Dohme Corp. | Methods for quantitating small RNA molecules |
| US7404969B2 (en) | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
| WO2006089340A2 (en) | 2005-02-23 | 2006-08-31 | V-Kardia Pty Ltd | Polynucleotide delivery to cardiac tissue |
| US20070065840A1 (en) | 2005-03-23 | 2007-03-22 | Irena Naguibneva | Novel oligonucleotide compositions and probe sequences useful for detection and analysis of microRNAS and their target mRNAS |
| WO2006111512A1 (en) | 2005-04-19 | 2006-10-26 | Basf Plant Science Gmbh | Improved methods controlling gene expression |
| PL2002003T3 (pl) | 2005-05-27 | 2016-06-30 | Ospedale San Raffaele Srl | Wektor genetyczny zawierający mi-RNA |
| CN101448942B (zh) | 2005-12-12 | 2014-04-23 | 北卡罗来纳大学查珀尔希尔分校 | 调节肌细胞增殖和分化的microrna |
| EP1966390A1 (en) | 2005-12-29 | 2008-09-10 | Exiqon A/S | Detection of tissue origin of cancer |
| EP2388327A1 (en) | 2006-01-27 | 2011-11-23 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and compositions for the use in modulation of micrornas |
| KR101407707B1 (ko) | 2006-04-03 | 2014-06-19 | 산타리스 팔마 에이/에스 | Ａｎｔｉ-ｍｉｒｎａ 안티센스 올리고뉴클레오타이드를 함유하는 약학적 조성물 |
| US8466117B2 (en) | 2006-07-28 | 2013-06-18 | The Johns Hopkins University | Compositions and methods for modulating angiogenesis |
| EP2434017A3 (en) | 2006-08-01 | 2012-09-05 | Board of Regents of the University of Texas System | Identification of a micro-RNA that activates expression of beta-myosin heavy chain |
| WO2008042231A2 (en) | 2006-09-29 | 2008-04-10 | Children's Medical Center Corporation | Compositions and methods for evaluating and treating heart failure |
| WO2008043521A2 (de) | 2006-10-09 | 2008-04-17 | Julius-Maximilians-Universität Würzburg | Microrna (mirna) zur diagnose und therapie von herzerkrankungen |
| WO2008147430A2 (en) | 2006-10-11 | 2008-12-04 | Nucleonics, Inc. | Microrna-formatted multitarget interfering rna vector constructs and methods of using the same |
| AU2007323469B2 (en) | 2006-11-23 | 2014-07-24 | Guangdong Maijinjia Biotechnology Co., Ltd | Oligonucleotides for modulating target RNA activity |
| US20100280094A1 (en) | 2006-12-14 | 2010-11-04 | Novartis Ag | Compositions and methods to treat muscular & cardiovascular disorders |
| EP3536788A1 (en) | 2006-12-21 | 2019-09-11 | QIAGEN GmbH | Microrna target site blocking oligos and uses thereof |
| US20090137504A1 (en) | 2006-12-21 | 2009-05-28 | Soren Morgenthaler Echwald | Microrna target site blocking oligos and uses thereof |
| DK2149605T3 (da) | 2007-03-22 | 2013-09-30 | Santaris Pharma As | Korte RNA antagonist forbindelser til modulering af det ønskede mRNA |
| US20090105174A1 (en) | 2007-04-20 | 2009-04-23 | Amgen Inc. | Nucleic acids hybridizable to micro rna and precursors thereof |
| US8841267B2 (en) | 2007-05-23 | 2014-09-23 | Ge Healthcare Dharmacon, Inc. | Micro-RNA scaffolds, non-naturally occurring micro-RNAs, and methods for optimizing non-naturally occurring micro-RNAs |
| WO2009018492A2 (en) | 2007-07-31 | 2009-02-05 | The Board Of Regents Of The University Of Texas System | Micro-rnas that control myosin expression and myofiber identity |
| WO2009026574A2 (en) | 2007-08-23 | 2009-02-26 | Keren Pharmaceutical, Inc. | Immunogenic compositions and uses thereof |
| US8455199B2 (en) | 2007-09-14 | 2013-06-04 | The Ohio State University Research Foundation | MicroRNA expression in human peripheral blood microvesicles and uses thereof |
| US8288356B2 (en) * | 2007-10-04 | 2012-10-16 | Santaris Pharma A/S | MicroRNAs |
| WO2009058818A2 (en) | 2007-10-29 | 2009-05-07 | The Board Of Regents Of The University Of Texas System | Compositions comprising a micro-rna and methods of their use in regulating cardiac remodeling |
| DE102007052114B4 (de) | 2007-10-30 | 2011-01-05 | T2Cure Gmbh | Verfahren zur Modulation der Funktion, des Wachstums oder der Differenzierung einer Zelle |
| CN101424640B (zh) | 2007-11-02 | 2012-07-25 | 江苏命码生物科技有限公司 | 血清中微小核糖核酸的检测方法和用于检测的试剂盒、生物芯片及其制作和应用方法 |
| CA2705325C (en) | 2007-11-09 | 2016-11-01 | The Board Of Regents Of The University Of Texas System | Micro-rnas of the mir-15 family modulate cardiomyocyte survival and cardiac repair |
| CA2711179A1 (en) | 2007-12-31 | 2009-07-16 | Nanocor Therapeutics, Inc. | Rna interference for the treatment of heart failure |
| EP2096171A1 (en) | 2008-02-27 | 2009-09-02 | Julius-Maximilians-Universität Würzburg | MicroRNA (miRNA) and down-stream targets for diagnostic and therapeutic purposes |
| EP2268811A1 (en) | 2008-03-07 | 2011-01-05 | Santaris Pharma A/S | Pharmaceutical compositions for treatment of microrna related diseases |
| US20110160285A1 (en) | 2008-03-13 | 2011-06-30 | The Regents Of The University Of Colorado | Identification of mirna profiles that are diagnostic of hypertrophic cardiomyopathy |
| US20090326049A1 (en) | 2008-04-04 | 2009-12-31 | Alexander Aristarkhov | Blocking oligos for inhibition of microrna and sirna activity and uses thereof |
| CA2726052A1 (en) | 2008-06-04 | 2009-12-10 | The Board Of Regents Of The University Of Texas System | Modulation of gene expression through endogenous small rna targeting of gene promoters |
| WO2009151600A2 (en) | 2008-06-10 | 2009-12-17 | Tufts University | Smad proteins control drosha-mediated mirna maturation |
| WO2010000665A1 (en) * | 2008-06-30 | 2010-01-07 | Santaris Pharma A/S | Antidote oligomers |
| CN101386848A (zh) | 2008-08-12 | 2009-03-18 | 南京大学 | 细胞微粒子所载微小核糖核酸及其制备研究方法和应用 |
| EP2346883B1 (en) | 2008-09-23 | 2016-03-23 | Scott G. Petersen | Self delivering bio-labile phosphate protected pro-oligos for oligonucleotide based therapeutics and mediating rna interference |
| WO2010048585A2 (en) | 2008-10-24 | 2010-04-29 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
| MX2011008190A (es) * | 2009-02-04 | 2011-10-06 | Univ Texas | Direccionamiento dual de mir-208 y mir-499 en el tratamiento de trastornos cardiacos. |
| WO2010093788A2 (en) | 2009-02-11 | 2010-08-19 | Dicerna Pharmaceuticals, Inc. | Multiplex dicer substrate rna interference molecules having joining sequences |
| JP5773535B2 (ja) * | 2009-04-24 | 2015-09-02 | ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブＲｏｃｈｅ Ｉｎｎｏｖａｔｉｏｎ Ｃｅｎｔｅｒ Ｃｏｐｅｎｈａｇｅｎ Ａ／Ｓ | インターフェロンに非応答性のｈｃｖ患者の治療のための医薬組成物 |
| DK2427472T3 (en) | 2009-05-05 | 2016-09-12 | Miragen Therapeutics | Lipophilic polynukleotidkonjugater |
| SG176716A1 (en) * | 2009-06-08 | 2012-01-30 | Miragen Therapeutics | CHEMICAL MODIFICATION MOTIFS FOR miRNA INHIBITORS AND MIMETICS |
| EP2475372B2 (en) | 2009-09-10 | 2020-10-21 | Velin-Pharma A/S | Method for the preparation of micro-rna and its therapeutic application |
| US9364495B2 (en) | 2009-10-20 | 2016-06-14 | Roche Innovation Center Copenhagen A/S | Oral delivery of therapeutically effective LNA oligonucleotides |
| US8592151B2 (en) | 2009-11-17 | 2013-11-26 | Musc Foundation For Research Development | Assessing left ventricular remodeling via temporal detection and measurement of microRNA in body fluids |
| US20130109738A1 (en) | 2010-02-24 | 2013-05-02 | The Board Of Trustees Of The Leland Stanford Junior University | Control of Cardiac Growth, Differentiation and Hypertrophy |
| WO2011117353A1 (en) | 2010-03-24 | 2011-09-29 | Mirrx Therapeutics A/S | Bivalent antisense oligonucleotides |
| US9821009B2 (en) | 2010-04-13 | 2017-11-21 | Jiangsu Mingma Biotech Co., Ltd. | Method for modulating microRNA content in living beings and the use thereof |
| EP2865765B1 (en) | 2010-04-20 | 2016-08-17 | Hummingbird Diagnostics GmbH | Complex miRNA sets as novel biomarkers for an acute coronary syndrome |
| WO2011139911A2 (en) | 2010-04-29 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Lipid formulated single stranded rna |
| WO2011154553A2 (en) | 2010-06-11 | 2011-12-15 | Cellartis Ab | Novel micrornas for the detection and isolaton of human embryonic stem cell-derived cardiac cell types |
| ITMI20101089A1 (it) | 2010-06-16 | 2011-12-17 | Istituto Naz Di Genetica Molecolare Ingm | Profili di espressione di micro-rna nel sangue periferico per il monitoraggio del sistema immunitario |
| US9987309B2 (en) | 2010-07-08 | 2018-06-05 | Duke University | Direct reprogramming of cells to cardiac myocyte fate |
| GB201012418D0 (en) * | 2010-07-23 | 2010-09-08 | Santaris Pharma As | Process |
| WO2012018866A2 (en) | 2010-08-03 | 2012-02-09 | University Of South Alabama | Methods and compositions for the diagnosis and treatment of breast cancer |
| JP2013537538A (ja) | 2010-08-13 | 2013-10-03 | ザ ユニバーシティ コート オブ ザ ユニバーシティ オブ グラスゴー | 微小水泡および関連するマイクロｒｎａの治療用途 |
| JP6106085B2 (ja) | 2010-08-24 | 2017-03-29 | サーナ・セラピューティクス・インコーポレイテッドＳｉｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | 内部非核酸スペーサーを含む一本鎖ＲＮＡｉ剤 |
| EP2616543A1 (en) * | 2010-09-15 | 2013-07-24 | Alnylam Pharmaceuticals, Inc. | MODIFIED iRNA AGENTS |
| AU2011323085B2 (en) * | 2010-11-05 | 2014-10-30 | Miragen Therapeutics | Base modified oligonucleotides |
| US8642751B2 (en) * | 2010-12-15 | 2014-02-04 | Miragen Therapeutics | MicroRNA inhibitors comprising locked nucleotides |
| WO2012149646A1 (en) | 2011-05-05 | 2012-11-08 | Sunnybrook Research Institute | Mirna inhibitors and their uses |
| US9428749B2 (en) | 2011-10-06 | 2016-08-30 | The Board Of Regents, The University Of Texas System | Control of whole body energy homeostasis by microRNA regulation |
| GB201117482D0 (en) | 2011-10-11 | 2011-11-23 | Univ Dundee | Targetiing of miRNA precursors |
| EP2584040A1 (en) | 2011-10-17 | 2013-04-24 | Pharmahungary 2000 Kft. | Compounds for treatment of ischemic injury |
| WO2013059496A1 (en) | 2011-10-18 | 2013-04-25 | Dicerna Pharmaceuticals, Inc. | Amine cationic lipids and uses thereof |
| CA2895077A1 (en) | 2011-12-12 | 2013-06-20 | Beverly Packard | In vivo delivery of oligonucleotides |
| EP2604690A1 (en) | 2011-12-15 | 2013-06-19 | Oncostamen S.r.l. | MicroRNAs and uses thereof |
| EP2816114A3 (en) | 2011-12-15 | 2015-02-25 | Oncostamen S.r.l. | MicroRNAs and uses thereof |
| FR2984358A1 (fr) | 2011-12-16 | 2013-06-21 | Genethon | Methodes pour le diagnostic de dystrophies musculaires |
| JP6208228B2 (ja) | 2012-06-21 | 2017-10-04 | ミラゲン セラピューティクス， インコーポレイテッド | ロックド核酸モチーフを含むオリゴヌクレオチドベースの阻害剤 |
| US9163235B2 (en) | 2012-06-21 | 2015-10-20 | MiRagen Therapeutics, Inc. | Inhibitors of the miR-15 family of micro-RNAs |
| EP2759595B1 (en) | 2013-01-24 | 2016-09-14 | Pierre Fabre Médicament S.A.S. | Composition comprising an encapsulated antagomir |
| EP3247716A4 (en) | 2015-01-20 | 2018-10-17 | Miragen Therapeutics, Inc. | Mir-92 inhibitors and uses thereof |
-
2013
- 2013-06-21 JP JP2015518626A patent/JP6208228B2/ja not_active Expired - Fee Related
- 2013-06-21 KR KR1020157000512A patent/KR101928418B1/ko not_active Expired - Fee Related
- 2013-06-21 US US13/924,340 patent/US9388408B2/en not_active Expired - Fee Related
- 2013-06-21 AU AU2013278011A patent/AU2013278011B2/en not_active Ceased
- 2013-06-21 CN CN201710249089.9A patent/CN107236735B/zh not_active Expired - Fee Related
- 2013-06-21 HK HK15110337.4A patent/HK1209781A1/xx unknown
- 2013-06-21 CN CN201380038840.0A patent/CN104685056A/zh active Pending
- 2013-06-21 ES ES18154472T patent/ES2801875T3/es active Active
- 2013-06-21 CA CA2876180A patent/CA2876180C/en not_active Expired - Fee Related
- 2013-06-21 DK DK18154472.7T patent/DK3354734T3/da active
- 2013-06-21 EP EP13807536.1A patent/EP2864482A4/en not_active Withdrawn
- 2013-06-21 MX MX2014015643A patent/MX355408B/es active IP Right Grant
- 2013-06-21 WO PCT/US2013/047157 patent/WO2013192576A2/en not_active Ceased
- 2013-06-21 EP EP18154472.7A patent/EP3354734B1/en active Active
-
2016
- 2016-05-13 US US15/154,711 patent/US9803202B2/en not_active Expired - Fee Related
-
2017
- 2017-09-06 JP JP2017171211A patent/JP2017217007A/ja active Pending
- 2017-09-13 US US15/703,753 patent/US10337005B2/en not_active Expired - Fee Related
-
2018
- 2018-03-22 HK HK18103977.1A patent/HK1244509A1/zh unknown
Non-Patent Citations (1)
| Title |
|---|
| Locked nucleic acid as a novel class of therapeutic agents;Rakesh N. Veedu等;《RNA Biology》;20090701;第6卷(第3期);第321-323页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013192576A3 (en) | 2014-04-03 |
| US9803202B2 (en) | 2017-10-31 |
| AU2013278011B2 (en) | 2018-09-20 |
| CA2876180C (en) | 2019-11-19 |
| CN107236735A (zh) | 2017-10-10 |
| US20160326526A1 (en) | 2016-11-10 |
| ES2801875T3 (es) | 2021-01-14 |
| JP2017217007A (ja) | 2017-12-14 |
| MX355408B (es) | 2018-04-18 |
| US20130344135A1 (en) | 2013-12-26 |
| AU2013278011A1 (en) | 2015-01-15 |
| WO2013192576A2 (en) | 2013-12-27 |
| EP2864482A4 (en) | 2016-02-10 |
| MX2014015643A (es) | 2015-07-17 |
| CN104685056A (zh) | 2015-06-03 |
| KR101928418B1 (ko) | 2018-12-12 |
| KR20150023687A (ko) | 2015-03-05 |
| JP6208228B2 (ja) | 2017-10-04 |
| EP2864482A2 (en) | 2015-04-29 |
| EP3354734A1 (en) | 2018-08-01 |
| CA2876180A1 (en) | 2013-12-27 |
| US9388408B2 (en) | 2016-07-12 |
| US10337005B2 (en) | 2019-07-02 |
| US20180273944A1 (en) | 2018-09-27 |
| HK1244509A1 (zh) | 2018-08-10 |
| EP3354734B1 (en) | 2020-06-10 |
| HK1209781A1 (en) | 2016-04-08 |
| DK3354734T3 (da) | 2020-06-29 |
| JP2015521626A (ja) | 2015-07-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107236735B (zh) | 包含锁核酸基序的基于寡核苷酸的抑制剂 | |
| CN102803284B (zh) | 用于miRNA抑制剂和模拟物的化学修饰基序 | |
| US9163235B2 (en) | Inhibitors of the miR-15 family of micro-RNAs | |
| KR20140004646A (ko) | 잠금 뉴클레오티드를 포함하는 마이크로rna 억제제 | |
| HK1259394A1 (en) | Oligonucleotide-based inhibitors comprising locked nucleic acid motif | |
| WO2020184700A1 (ja) | Ｉｈｈ発現を調節するための核酸複合体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1244509 Country of ref document: HK |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20191108 Termination date: 20210621 |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1244509 Country of ref document: HK |