CA2876105A1 - Inhibitors of the mir-15 family of micro-rnas - Google Patents
Inhibitors of the mir-15 family of micro-rnas Download PDFInfo
- Publication number
- CA2876105A1 CA2876105A1 CA2876105A CA2876105A CA2876105A1 CA 2876105 A1 CA2876105 A1 CA 2876105A1 CA 2876105 A CA2876105 A CA 2876105A CA 2876105 A CA2876105 A CA 2876105A CA 2876105 A1 CA2876105 A1 CA 2876105A1
- Authority
- CA
- Canada
- Prior art keywords
- oligonucleotide
- mir
- nucleotides
- seq
- locked
- 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.)
- Abandoned
Links
- 108091057645 miR-15 stem-loop Proteins 0.000 title claims abstract description 111
- 108091070501 miRNA Proteins 0.000 title claims abstract description 61
- 239000003112 inhibitor Substances 0.000 title claims description 120
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 168
- 108091031326 miR-15b stem-loop Proteins 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 28
- 108091027943 miR-16 stem-loop Proteins 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 108091030938 miR-424 stem-loop Proteins 0.000 claims abstract description 17
- 108091063340 miR-497 stem-loop Proteins 0.000 claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 15
- 125000001921 locked nucleotide group Chemical group 0.000 claims description 64
- 125000003729 nucleotide group Chemical group 0.000 claims description 61
- 239000002773 nucleotide Substances 0.000 claims description 59
- 230000000694 effects Effects 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 35
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 24
- 210000004027 cell Anatomy 0.000 claims description 21
- 239000011780 sodium chloride Substances 0.000 claims description 21
- 210000005003 heart tissue Anatomy 0.000 claims description 18
- 238000000338 in vitro Methods 0.000 claims description 15
- 238000001727 in vivo Methods 0.000 claims description 14
- 208000010125 myocardial infarction Diseases 0.000 claims description 14
- 238000002347 injection Methods 0.000 claims description 12
- 239000007924 injection Substances 0.000 claims description 12
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 12
- 206010019280 Heart failures Diseases 0.000 claims description 11
- 230000000295 complement effect Effects 0.000 claims description 11
- 238000003670 luciferase enzyme activity assay Methods 0.000 claims description 11
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 10
- 208000006029 Cardiomegaly Diseases 0.000 claims description 10
- 206010063837 Reperfusion injury Diseases 0.000 claims description 10
- 230000000747 cardiac effect Effects 0.000 claims description 10
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 9
- 238000007920 subcutaneous administration Methods 0.000 claims description 9
- 238000007918 intramuscular administration Methods 0.000 claims description 7
- 208000028867 ischemia Diseases 0.000 claims description 7
- 239000000693 micelle Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 239000002502 liposome Substances 0.000 claims description 5
- 230000001575 pathological effect Effects 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000001475 halogen functional group Chemical group 0.000 claims description 4
- 210000004962 mammalian cell Anatomy 0.000 claims description 4
- 238000007911 parenteral administration Methods 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 238000007912 intraperitoneal administration Methods 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 238000002054 transplantation Methods 0.000 claims description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- 239000011324 bead Substances 0.000 claims description 2
- 238000001246 colloidal dispersion Methods 0.000 claims description 2
- 238000013270 controlled release Methods 0.000 claims description 2
- 230000003111 delayed effect Effects 0.000 claims description 2
- 210000002064 heart cell Anatomy 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
- 239000004005 microsphere Substances 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 238000011808 rodent model Methods 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 238000013268 sustained release Methods 0.000 claims description 2
- 239000012730 sustained-release form Substances 0.000 claims description 2
- 101150056413 Pim1 gene Proteins 0.000 claims 1
- 239000002088 nanocapsule Substances 0.000 claims 1
- 239000007764 o/w emulsion Substances 0.000 claims 1
- 239000002679 microRNA Substances 0.000 abstract description 46
- 230000014509 gene expression Effects 0.000 abstract description 37
- 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 Chemical class 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 abstract description 27
- -1 miR-15a Proteins 0.000 abstract description 18
- 230000008901 benefit Effects 0.000 abstract description 5
- 230000001988 toxicity Effects 0.000 abstract description 4
- 231100000419 toxicity Toxicity 0.000 abstract description 4
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 description 30
- 230000004048 modification Effects 0.000 description 28
- 238000012986 modification Methods 0.000 description 28
- 241000700159 Rattus Species 0.000 description 23
- 241000699670 Mus sp. Species 0.000 description 20
- 238000003753 real-time PCR Methods 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 15
- 238000011282 treatment Methods 0.000 description 15
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 14
- 238000009472 formulation Methods 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 12
- 108091033319 polynucleotide Proteins 0.000 description 10
- 102000040430 polynucleotide Human genes 0.000 description 10
- 239000002157 polynucleotide Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 208000035657 Abasia Diseases 0.000 description 9
- 230000009977 dual effect Effects 0.000 description 9
- 230000003389 potentiating effect Effects 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- 101150115284 BIRC5 gene Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000000692 anti-sense effect Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000011552 rat model Methods 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- 108700011259 MicroRNAs Proteins 0.000 description 5
- 101710163270 Nuclease Proteins 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- CGPPXVAUDMUIPK-UHFFFAOYSA-N phosphoric acid trihydroxy(sulfanylidene)-lambda5-phosphane Chemical compound OP(O)(O)=O.OP(O)(O)=S CGPPXVAUDMUIPK-UHFFFAOYSA-N 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 239000002719 pyrimidine nucleotide Substances 0.000 description 4
- 150000003230 pyrimidines Chemical class 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 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
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000009787 cardiac fibrosis Effects 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000003966 vascular damage Effects 0.000 description 3
- 230000002861 ventricular Effects 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 241000023308 Acca Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 101100271190 Plasmodium falciparum (isolate 3D7) ATAT gene Proteins 0.000 description 2
- 230000004570 RNA-binding Effects 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
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound 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 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
- 230000000712 assembly Effects 0.000 description 2
- 238000000429 assembly Methods 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 108091074057 miR-16-1 stem-loop Proteins 0.000 description 2
- 108091056204 miR-16-2 stem-loop Proteins 0.000 description 2
- 238000003253 miRNA assay Methods 0.000 description 2
- 238000002493 microarray Methods 0.000 description 2
- 230000004001 molecular interaction Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000011809 primate model Methods 0.000 description 2
- 239000002213 purine nucleotide Substances 0.000 description 2
- 239000002510 pyrogen Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 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
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 108010017009 CD11b Antigen Proteins 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 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
- 108020004414 DNA Proteins 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 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
- 108060003393 Granulin Proteins 0.000 description 1
- 101000608672 Homo sapiens Uveal autoantigen with coiled-coil domains and ankyrin repeats Proteins 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
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 108091092539 MiR-208 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
- 238000010222 PCR analysis Methods 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108010052090 Renilla Luciferases Proteins 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
- 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 102100039543 Uveal autoantigen with coiled-coil domains and ankyrin repeats Human genes 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229960005305 adenosine 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
- 238000000540 analysis of variance Methods 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 229940124345 antianginal agent Drugs 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000000504 antifibrinolytic agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 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
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 239000000480 calcium channel blocker Substances 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
- 230000003683 cardiac damage Effects 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 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
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000004074 complement inhibitor Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 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
- 238000005315 distribution function Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000001094 effect on targets Effects 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 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
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- PLHJDBGFXBMTGZ-WEVVVXLNSA-N furazolidone Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)OCC1 PLHJDBGFXBMTGZ-WEVVVXLNSA-N 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
- 230000004547 gene signature Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 102000017941 granulin Human genes 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
- 239000003667 hormone antagonist Substances 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
- 238000001802 infusion Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940028435 intralipid Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000002960 lipid emulsion Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 229940080194 liposyn iii Drugs 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108091062762 miR-21 stem-loop Proteins 0.000 description 1
- 108091041631 miR-21-1 stem-loop Proteins 0.000 description 1
- 108091044442 miR-21-2 stem-loop Proteins 0.000 description 1
- 108091059493 miR-322 stem-loop Proteins 0.000 description 1
- 108091056170 miR-499 stem-loop Proteins 0.000 description 1
- 108091050885 miR-499-1 stem-loop Proteins 0.000 description 1
- 108091038523 miR-499-2 stem-loop Proteins 0.000 description 1
- 108091007426 microRNA precursor Proteins 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- YIEDSISPYKQADU-UHFFFAOYSA-N n-acetyl-n-[2-methyl-4-[(2-methylphenyl)diazenyl]phenyl]acetamide Chemical compound C1=C(C)C(N(C(C)=O)C(=O)C)=CC=C1N=NC1=CC=CC=C1C YIEDSISPYKQADU-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 238000011457 non-pharmacological treatment Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 229940064696 nutrilipid Drugs 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
- 230000002018 overexpression Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 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
- 108091007428 primary miRNA Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium 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
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 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
- 239000005451 thionucleotide Substances 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 230000007704 transition Effects 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
- 210000005166 vasculature Anatomy 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C12N2310/32—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
- C12N2310/344—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
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261662772P | 2012-06-21 | 2012-06-21 | |
| US61/662,772 | 2012-06-21 | ||
| US201361780352P | 2013-03-13 | 2013-03-13 | |
| US61/780,352 | 2013-03-13 | ||
| PCT/US2013/046960 WO2013192486A1 (en) | 2012-06-21 | 2013-06-21 | Inhibitors of the mir-15 family of micro-rnas |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2876105A1 true CA2876105A1 (en) | 2013-12-27 |
Family
ID=49769409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2876105A Abandoned CA2876105A1 (en) | 2012-06-21 | 2013-06-21 | Inhibitors of the mir-15 family of micro-rnas |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US9163235B2 (enExample) |
| EP (1) | EP2863956A4 (enExample) |
| JP (1) | JP2015525081A (enExample) |
| KR (1) | KR20150036140A (enExample) |
| CN (1) | CN104540527A (enExample) |
| AR (1) | AR091539A1 (enExample) |
| AU (1) | AU2013277033A1 (enExample) |
| BR (1) | BR112014032239A2 (enExample) |
| CA (1) | CA2876105A1 (enExample) |
| EA (1) | EA201590070A1 (enExample) |
| HK (1) | HK1209621A1 (enExample) |
| IN (1) | IN2014DN10899A (enExample) |
| MD (1) | MD20150006A2 (enExample) |
| MX (1) | MX2014015641A (enExample) |
| SG (1) | SG11201408460UA (enExample) |
| TW (1) | TW201406774A (enExample) |
| WO (1) | WO2013192486A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HK1209781A1 (en) | 2012-06-21 | 2016-04-08 | MiRagen Therapeutics, Inc. | Oligonucleotide-based inhibitors comprising locked nucleic acid motif |
| EP2970968B1 (en) | 2013-03-15 | 2018-01-10 | Miragen Therapeutics, Inc. | Bridged bicyclic nucleosides |
| US10443044B2 (en) | 2014-04-17 | 2019-10-15 | Ips Heart | Generating cardiac progenitor cells from pluripotent stem cells using isoxazole or isoxazole like compounds |
| TW201614069A (en) | 2014-08-04 | 2016-04-16 | Miragen Therapeutics Inc | Inhibitors of MYH7B and uses thereof |
| EP3177721A1 (en) | 2014-08-07 | 2017-06-14 | Regulus Therapeutics Inc. | Targeting micrornas for metabolic disorders |
| CN107636003A (zh) | 2015-01-20 | 2018-01-26 | 米拉根医疗股份有限公司 | miR‑92抑制剂及其用途 |
| 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 |
| CN110177544A (zh) | 2016-11-29 | 2019-08-27 | 普尔泰克健康有限公司 | 用于递送治疗剂的外泌体 |
| CN106692175A (zh) * | 2016-12-26 | 2017-05-24 | 大连医科大学附属第二医院 | miR‑665‑3p抑制物在制备防治缺血再灌注损伤药物中的应用 |
| US10941403B2 (en) | 2018-04-02 | 2021-03-09 | Oregon Health & Science University | Microrna inhibitors as anti-cancer therapeutics |
| EP4005602A4 (en) | 2019-07-30 | 2024-06-12 | Shionogi & Co., Ltd | NUCLEIC ACID AGENT TARGETED AGAINST MURF1 |
| CN116438305A (zh) * | 2020-07-23 | 2023-07-14 | 法兰克福大学 | 用于治疗心力衰竭的miRNA的组合抑制 |
| CN113599540B (zh) * | 2021-05-27 | 2023-05-23 | 山西医科大学 | miRNA-195-5p在制备抑制或降低麦芽酚铝所致神经细胞损伤的试剂中的应用 |
Family Cites Families (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2390328A1 (en) | 2001-09-28 | 2011-11-30 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | MicroRNA molecules |
| SI1504126T1 (sl) | 2002-05-03 | 2014-08-29 | Duke University Office Of Science And Technology | Postopek regulacije izraĹľanja genov |
| US7892793B2 (en) | 2002-11-04 | 2011-02-22 | University Of Massachusetts | Allele-specific RNA interference |
| EP1567007B1 (en) | 2002-11-13 | 2012-02-22 | Thomas Jefferson University | Compositions and methods for cancer diagnosis and therapy |
| US7482117B2 (en) | 2002-12-20 | 2009-01-27 | Celera Corporation | Genetic polymorphisms associated with myocardial infarction, methods of detection and uses thereof |
| JP2006519008A (ja) | 2003-02-10 | 2006-08-24 | 独立行政法人産業技術総合研究所 | 哺乳動物細胞の調節 |
| WO2005017111A2 (en) | 2003-07-15 | 2005-02-24 | The Trustees Of The University Of Pennsylvania | Methods and systems for identifying micro-rna targets and synthesizing novel micro-rnas and uses of the same |
| EP2530157B1 (en) | 2003-07-31 | 2016-09-28 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of miRNAs |
| US8106180B2 (en) | 2003-08-07 | 2012-01-31 | Whitehead Institute For Biomedical Research | Methods and products for expression of micro RNAs |
| 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 |
| WO2005028648A1 (ja) | 2003-09-22 | 2005-03-31 | Aichi Prefecture | リンパ腫の病型および予後診断方法 |
| CA2539654A1 (en) | 2003-10-14 | 2005-05-06 | Novartis Ag | Oligonucleotide microarray |
| CA2545944A1 (en) | 2003-11-13 | 2005-06-02 | Board Of Regents, The University Of Texas System | Inhibition of trp channels as a treatment for cardiac hypertrophy and heart failure |
| WO2005056797A1 (en) | 2003-12-15 | 2005-06-23 | Kye-Seong Kim | Novel mirna molecules isolated from human embryonic stem cell |
| WO2005078139A2 (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 |
| US8088902B2 (en) | 2004-04-05 | 2012-01-03 | The Rockefeller University | DNA virus microRNA and methods for inhibiting same |
| US20050260648A1 (en) | 2004-04-06 | 2005-11-24 | Huffel Christophe V | Method for the determination of cellular transcriptional |
| US20060134639A1 (en) | 2004-04-06 | 2006-06-22 | Huffel Christophe V | Method for the determination of cellular transcriptional regulation |
| CA2562390C (en) | 2004-04-07 | 2014-12-02 | Exiqon A/S | Novel methods for quantification of micrornas and small interfering rnas |
| EP2474616B1 (en) | 2004-05-28 | 2015-07-08 | Asuragen, Inc. | Methods and compositions involving microRNA |
| US7582744B2 (en) | 2004-08-10 | 2009-09-01 | Alnylam Pharmaceuticals, Inc. | Chemically modified oligonucleotides |
| AU2005282731B2 (en) | 2004-09-02 | 2010-04-01 | Yale University | Regulation of oncogenes by microRNAs |
| FR2877350B1 (fr) | 2004-11-03 | 2010-08-27 | Centre Nat Rech Scient | IDENTIFICATION ET UTILISATION DE miRNAs IMPLIQUES DANS LA DIFFERENCIATION DE CELLULES ISSUES D'UNE LEUCEMIE MYELOIDE |
| EP1838852A2 (en) | 2004-11-12 | 2007-10-03 | 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 |
| WO2006071884A2 (en) | 2004-12-27 | 2006-07-06 | The Regents Of The University Of Michigan | Oligonucleotide based therapeutics |
| 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 |
| 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 |
| JP2006292367A (ja) | 2005-04-05 | 2006-10-26 | Mitsubishi Rayon Co Ltd | ｍｉＲＮＡ検出用マイクロアレイ |
| WO2006108582A2 (en) | 2005-04-15 | 2006-10-19 | Cenix Bioscience Gmbh | Human marker genes and agents for diagnosis, treatment and prophylaxis of cardiovascular disorders and artherosclerosis |
| BRPI0608829A2 (pt) | 2005-04-19 | 2011-03-15 | Basf Plant Science Gmbh | método para a expressão transgênica com especificidade intensificada em uma planta, uso de um construto de ácido nucleico quimérico, seqüência de ribonucleotìdeo quimérica, construto de expressão, vetor de expressão, organismo não-humano ou célula transformada, semente transformada, e, preparação farmacêutica |
| KR20130114758A (ko) | 2005-05-27 | 2013-10-17 | 오스페달레 산 라파엘 에스.알.엘. | Ｍｉ-ｒｎａ를 포함하는 유전자 벡터 |
| WO2007053184A2 (en) | 2005-05-31 | 2007-05-10 | Cold Spring Harbor Laboratory | Methods for producing micrornas |
| US20070054287A1 (en) | 2005-05-31 | 2007-03-08 | Applera Corporation | Method for identifying medically important cell populations using micro rna as tissue specific biomarkers |
| US20090209621A1 (en) | 2005-06-03 | 2009-08-20 | The Johns Hopkins University | Compositions and methods for decreasing microrna expression for the treatment of neoplasia |
| US20070213292A1 (en) | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
| EP1919512B1 (en) | 2005-08-10 | 2014-11-12 | Alnylam Pharmaceuticals Inc. | Chemically modified oligonucleotides for use in modulating micro rna and uses thereof |
| CN101426912A (zh) | 2005-08-17 | 2009-05-06 | 瑟纳治疗公司 | 介导rna干扰的化学修饰短干扰核酸分子 |
| WO2007033023A2 (en) | 2005-09-12 | 2007-03-22 | The Ohio State University Research Foundation | Compositions and methods for the diagnosis and therapy of bcl2-associated cancers |
| US20070092882A1 (en) | 2005-10-21 | 2007-04-26 | Hui Wang | Analysis of microRNA |
| EP1951736A4 (en) | 2005-11-21 | 2009-12-16 | Johnson & Johnson Res Pty Ltd | INTERFERING MULTICIBLATION RNA AND METHODS OF USE AND DESIGN |
| WO2007087451A2 (en) | 2006-01-25 | 2007-08-02 | University Of Massachusetts | Compositions and methods for enhancing discriminatory rna interference |
| WO2007092181A2 (en) | 2006-01-26 | 2007-08-16 | Unversity Of Massachusetts | Compositions and methods for modulating translational repression |
| WO2007089607A2 (en) | 2006-01-26 | 2007-08-09 | University Of Massachusetts | Rna silencing agents for use in therapy and nanotransporters for efficient delivery of same |
| JP5213723B2 (ja) | 2006-01-27 | 2013-06-19 | アイシス ファーマシューティカルズ， インコーポレーテッド | マイクロｒｎａの調節に使用するためのオリゴマー化合物及び組成物 |
| WO2007095387A2 (en) | 2006-02-17 | 2007-08-23 | Dharmacon, Inc. | Compositions and methods for inhibiting gene silencing by rna interference |
| EP2522749A1 (en) | 2006-03-02 | 2012-11-14 | The Ohio State University | MicroRNA expression profile associated with pancreatic cancer |
| MX2008012219A (es) * | 2006-04-03 | 2008-10-02 | Santaris Pharma As | Composicion farmaceutica que comprende oligonucleotidos antisentido anti-miarn. |
| US20080220423A1 (en) | 2006-05-19 | 2008-09-11 | Soren Moller | Oligonucleotide probes useful for detection and analysis of microRNA precursors |
| WO2007147067A2 (en) | 2006-06-14 | 2007-12-21 | Rosetta Inpharmatics Llc | Methods and compositions for regulating cell cycle progression |
| WO2007147409A2 (en) | 2006-06-19 | 2007-12-27 | Københavns Universitet | Ribozyme mediated stabilization of polynucleotides |
| WO2008024499A2 (en) | 2006-08-25 | 2008-02-28 | Duke University | Methods for in vivo identification of endogenous mrna targets of micrornas |
| CA2663962A1 (en) | 2006-09-19 | 2008-03-27 | Asuragen, Inc. | Mir-15, mir-26, mir-31,mir-145, mir-147, mir-188, mir-215, mir-216, mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention |
| US20090306181A1 (en) | 2006-09-29 | 2009-12-10 | Children's Medical Center Corporation | Compositions and methods for evaluating and treating heart failure |
| EP2094869B1 (de) | 2006-10-09 | 2012-07-25 | 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 |
| US20100021914A1 (en) | 2006-11-23 | 2010-01-28 | Querdenker Aps | Oligonucleotides for modulating target rna activity |
| CA2671296A1 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Mir-126 regulated genes and pathways as targets for therapeutic intervention |
| WO2008073923A2 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Mirna regulated genes and pathways as targets for therapeutic intervention |
| EP2104735A2 (en) | 2006-12-08 | 2009-09-30 | Asuragen, INC. | Mir-21 regulated genes and pathways as targets for therapeutic intervention |
| DK2104737T3 (da) | 2006-12-08 | 2013-05-27 | Asuragen Inc | Funktioner og formål for let-7 mikro-RNAer |
| US20090137504A1 (en) | 2006-12-21 | 2009-05-28 | Soren Morgenthaler Echwald | Microrna target site blocking oligos and uses thereof |
| EP2113567B1 (en) | 2006-12-21 | 2019-04-03 | QIAGEN GmbH | MicroRNA target site blocking oligos and uses thereof |
| CA2671270A1 (en) | 2006-12-29 | 2008-07-17 | Asuragen, Inc. | Mir-16 regulated genes and pathways as targets for therapeutic intervention |
| US20080287383A1 (en) | 2007-03-02 | 2008-11-20 | Nastech Pharmaceutical Company Inc. | Nucleic acid compounds for inhibiting erbb gene expression and uses thereof |
| WO2008112226A2 (en) | 2007-03-13 | 2008-09-18 | Massachusetts Institute Of Technology | Cre-lox based gene knockdown constructs and methods of use thereof |
| EP2136846A4 (en) | 2007-03-26 | 2011-04-13 | Crc For Asthma And Airways Ltd | THERAPEUTIC OBJECTIVES AND MOLECULES |
| CA2687336C (en) | 2007-05-23 | 2014-12-23 | Dharmacon, Inc. | Micro-rna scaffolds and non-naturally occurring micro-rnas |
| CN101802227B (zh) | 2007-07-18 | 2014-12-10 | 科罗拉多大学董事会法人团体 | 非衰竭与衰竭的人心脏中微小rna的差异表达 |
| WO2009012263A2 (en) | 2007-07-18 | 2009-01-22 | The Trustees Of Columbia University In The City Of New York | Tissue-specific micrornas and compositions and uses thereof |
| US20090092980A1 (en) | 2007-07-20 | 2009-04-09 | Christoph Arenz | miRNA PROCESSING INHIBITOR EFFICACY ASSAYS AND SUBSTANCES |
| WO2009044895A1 (ja) | 2007-10-03 | 2009-04-09 | Kyowa Hakko Kirin Co., Ltd. | 標的遺伝子の発現を抑制する組成物 |
| ES2406686T3 (es) | 2007-10-04 | 2013-06-07 | Santaris Pharma A/S | Micromirs |
| 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 |
| US8389485B2 (en) | 2007-10-29 | 2013-03-05 | University Of Massachusetts | Encapsulated nanoparticles for nucleic acid delivery |
| EP2219653B1 (en) | 2007-11-09 | 2016-12-21 | The Board of Regents of The University of Texas System | Micro-rnas of the mir-15 family modulate cardiomyocyte survival and cardiac repair |
| US20100240058A1 (en) * | 2007-11-23 | 2010-09-23 | Panagene Inc. | MicroRNA Antisense PNAs, Compositions Comprising the Same, and Methods for Using and Evaluating the Same |
| EP2268811A1 (en) | 2008-03-07 | 2011-01-05 | Santaris Pharma A/S | Pharmaceutical compositions for treatment of microrna related diseases |
| EP2279267A4 (en) | 2008-03-27 | 2012-01-18 | Vascular Biosciences Inc | METHOD FOR IDENTIFYING NEW THERAPY CANDIDATES ON GENE EXPRESSION ANALYSIS IN DISEASES RELATED TO VACCINES |
| EP2105145A1 (en) | 2008-03-27 | 2009-09-30 | ETH Zürich | Method for muscle-specific delivery lipid-conjugated oligonucleotides |
| US20090326049A1 (en) | 2008-04-04 | 2009-12-31 | Alexander Aristarkhov | Blocking oligos for inhibition of microrna and sirna activity and uses thereof |
| US20100113284A1 (en) | 2008-04-04 | 2010-05-06 | Alexander Aristarkhov | Small interfering rna (sirna) target site blocking oligos and uses thereof |
| WO2009137807A2 (en) | 2008-05-08 | 2009-11-12 | Asuragen, Inc. | Compositions and methods related to mirna modulation of neovascularization or angiogenesis |
| WO2009149182A1 (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 |
| WO2010036939A2 (en) | 2008-09-26 | 2010-04-01 | University Of Southern California | A system for synergistic expression of multiple small functional rna elements |
| US8987435B2 (en) | 2008-10-24 | 2015-03-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
| WO2010126355A1 (en) | 2009-04-29 | 2010-11-04 | Academisch Medisch Centrum Bij De Universiteit Van Amsterdam | Means and methods for counteracting, preventing and/or determining heart failure, or a risk of heart failure |
| MA33488B1 (fr) | 2009-06-08 | 2012-08-01 | Miragen Therapeutics | Motifs de modification chimique pour des inhibiteurs et mimétiques de miarn |
-
2013
- 2013-06-19 US US13/921,537 patent/US9163235B2/en not_active Expired - Fee Related
- 2013-06-21 MD MDA20150006A patent/MD20150006A2/ro not_active Application Discontinuation
- 2013-06-21 CN CN201380039961.7A patent/CN104540527A/zh active Pending
- 2013-06-21 BR BR112014032239A patent/BR112014032239A2/pt not_active IP Right Cessation
- 2013-06-21 EA EA201590070A patent/EA201590070A1/ru unknown
- 2013-06-21 HK HK15110356.0A patent/HK1209621A1/xx unknown
- 2013-06-21 WO PCT/US2013/046960 patent/WO2013192486A1/en not_active Ceased
- 2013-06-21 EP EP13806131.2A patent/EP2863956A4/en not_active Withdrawn
- 2013-06-21 AU AU2013277033A patent/AU2013277033A1/en not_active Abandoned
- 2013-06-21 IN IN10899DEN2014 patent/IN2014DN10899A/en unknown
- 2013-06-21 TW TW102122289A patent/TW201406774A/zh unknown
- 2013-06-21 CA CA2876105A patent/CA2876105A1/en not_active Abandoned
- 2013-06-21 JP JP2015518597A patent/JP2015525081A/ja active Pending
- 2013-06-21 MX MX2014015641A patent/MX2014015641A/es unknown
- 2013-06-21 SG SG11201408460UA patent/SG11201408460UA/en unknown
- 2013-06-21 KR KR1020157001535A patent/KR20150036140A/ko not_active Withdrawn
- 2013-06-24 AR ARP130102219 patent/AR091539A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX2014015641A (es) | 2015-07-14 |
| AU2013277033A1 (en) | 2015-01-22 |
| KR20150036140A (ko) | 2015-04-07 |
| TW201406774A (zh) | 2014-02-16 |
| SG11201408460UA (en) | 2015-01-29 |
| IN2014DN10899A (enExample) | 2015-09-11 |
| HK1209621A1 (en) | 2016-04-08 |
| JP2015525081A (ja) | 2015-09-03 |
| MD20150006A2 (ro) | 2015-06-30 |
| US20130345288A1 (en) | 2013-12-26 |
| EP2863956A4 (en) | 2016-01-20 |
| AR091539A1 (es) | 2015-02-11 |
| CN104540527A (zh) | 2015-04-22 |
| EP2863956A1 (en) | 2015-04-29 |
| EA201590070A1 (ru) | 2015-04-30 |
| BR112014032239A2 (pt) | 2017-08-01 |
| WO2013192486A1 (en) | 2013-12-27 |
| US9163235B2 (en) | 2015-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9163235B2 (en) | Inhibitors of the miR-15 family of micro-RNAs | |
| US10337005B2 (en) | Oligonucleotide-based inhibitors comprising locked nucleic acid motif | |
| CN102803284B (zh) | 用于miRNA抑制剂和模拟物的化学修饰基序 | |
| US8642751B2 (en) | MicroRNA inhibitors comprising locked nucleotides | |
| CA2751489A1 (en) | Dual targeting of mir-208 and mir-499 in the treatment of cardiac disorders | |
| HK1259394A1 (en) | Oligonucleotide-based inhibitors comprising locked nucleic acid motif |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20190621 |