JP6637961B2 - Ｍｙｈ７ｂの阻害剤およびその使用 - Google Patents
Ｍｙｈ７ｂの阻害剤およびその使用 Download PDFInfo
- Publication number
- JP6637961B2 JP6637961B2 JP2017506382A JP2017506382A JP6637961B2 JP 6637961 B2 JP6637961 B2 JP 6637961B2 JP 2017506382 A JP2017506382 A JP 2017506382A JP 2017506382 A JP2017506382 A JP 2017506382A JP 6637961 B2 JP6637961 B2 JP 6637961B2
- Authority
- JP
- Japan
- Prior art keywords
- antisense oligonucleotide
- nucleotides
- myh7b
- sequence
- inhibitor
- 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
- 239000003112 inhibitor Substances 0.000 title claims description 290
- 101000958744 Homo sapiens Myosin-7B Proteins 0.000 title claims description 234
- 102100038322 Myosin-7B Human genes 0.000 title claims description 234
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 349
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 341
- 108091034117 Oligonucleotide Proteins 0.000 claims description 340
- 125000003729 nucleotide group Chemical group 0.000 claims description 222
- 239000002773 nucleotide Substances 0.000 claims description 203
- 230000000295 complement effect Effects 0.000 claims description 75
- 230000004048 modification Effects 0.000 claims description 48
- 238000012986 modification Methods 0.000 claims description 48
- 239000000203 mixture Substances 0.000 claims description 42
- 235000000346 sugar Nutrition 0.000 claims description 36
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 claims description 30
- 125000001921 locked nucleotide group Chemical group 0.000 claims description 29
- 108091056170 miR-499 stem-loop Proteins 0.000 claims description 29
- 108091050885 miR-499-1 stem-loop Proteins 0.000 claims description 29
- 108091038523 miR-499-2 stem-loop Proteins 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 27
- 230000001575 pathological effect Effects 0.000 claims description 27
- 208000006029 Cardiomegaly Diseases 0.000 claims description 26
- 108090000623 proteins and genes Proteins 0.000 claims description 26
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- 108091071651 miR-208 stem-loop Proteins 0.000 claims description 22
- 108091084446 miR-208a stem-loop Proteins 0.000 claims description 22
- 108091062547 miR-208a-1 stem-loop Proteins 0.000 claims description 22
- 108091055375 miR-208a-2 stem-loop Proteins 0.000 claims description 22
- 108091047268 miR-208b stem-loop Proteins 0.000 claims description 21
- 206010019280 Heart failures Diseases 0.000 claims description 19
- 229940124597 therapeutic agent Drugs 0.000 claims description 19
- 108010051583 Ventricular Myosins Proteins 0.000 claims description 17
- 208000010125 myocardial infarction Diseases 0.000 claims description 17
- -1 miR-15a Proteins 0.000 claims description 15
- 125000002652 ribonucleotide group Chemical group 0.000 claims description 15
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 13
- 125000002637 deoxyribonucleotide group Chemical group 0.000 claims description 12
- 230000035772 mutation Effects 0.000 claims description 12
- 239000005547 deoxyribonucleotide Substances 0.000 claims description 10
- 108091028664 Ribonucleotide Proteins 0.000 claims description 9
- 108091027943 miR-16 stem-loop Proteins 0.000 claims description 9
- 239000002336 ribonucleotide Substances 0.000 claims description 9
- 125000001475 halogen functional group Chemical group 0.000 claims description 8
- 108091031326 miR-15b stem-loop Proteins 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000005977 Ethylene Substances 0.000 claims description 5
- KPPPLADORXGUFI-KCRXGDJASA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(1-hydroxyethyl)oxolan-2-yl]pyrimidin-2-one Chemical group O[C@@H]1[C@H](O)[C@@H](C(O)C)O[C@H]1N1C(=O)N=C(N)C=C1 KPPPLADORXGUFI-KCRXGDJASA-N 0.000 claims description 3
- DEFLNOSTNCSZRB-IDTAVKCVSA-N 9-[(2r,3r,4r,5r)-3,4-dimethoxy-5-(methoxymethyl)oxolan-2-yl]-n-methoxypurin-6-amine Chemical compound CO[C@@H]1[C@H](OC)[C@@H](COC)O[C@H]1N1C2=NC=NC(NOC)=C2N=C1 DEFLNOSTNCSZRB-IDTAVKCVSA-N 0.000 claims 1
- 230000014509 gene expression Effects 0.000 description 70
- 108020004999 messenger RNA Proteins 0.000 description 55
- 238000000034 method Methods 0.000 description 52
- 230000000694 effects Effects 0.000 description 47
- 239000004055 small Interfering RNA Substances 0.000 description 40
- 210000002064 heart cell Anatomy 0.000 description 39
- 150000001875 compounds Chemical class 0.000 description 36
- 210000004413 cardiac myocyte Anatomy 0.000 description 35
- 150000007523 nucleic acids Chemical class 0.000 description 29
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 28
- 101100025407 Homo sapiens MYH7B gene Proteins 0.000 description 28
- 102000039446 nucleic acids Human genes 0.000 description 28
- 108020004707 nucleic acids Proteins 0.000 description 28
- 108020004459 Small interfering RNA Proteins 0.000 description 22
- 108091027967 Small hairpin RNA Proteins 0.000 description 21
- 101150018614 MYH7B gene Proteins 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 20
- 108091023037 Aptamer Proteins 0.000 description 18
- 208000019622 heart disease Diseases 0.000 description 18
- 230000005764 inhibitory process Effects 0.000 description 18
- 230000001105 regulatory effect Effects 0.000 description 18
- 108090000994 Catalytic RNA Proteins 0.000 description 16
- 102000053642 Catalytic RNA Human genes 0.000 description 16
- 108091092562 ribozyme Proteins 0.000 description 16
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 14
- 208000020446 Cardiac disease Diseases 0.000 description 14
- 108060008487 Myosin Proteins 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 230000008685 targeting Effects 0.000 description 14
- 102000003505 Myosin Human genes 0.000 description 13
- 230000002401 inhibitory effect Effects 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 12
- 238000001890 transfection Methods 0.000 description 12
- 239000013598 vector Substances 0.000 description 12
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 11
- 230000000747 cardiac effect Effects 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 238000003753 real-time PCR Methods 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 108010084498 Myosin Heavy Chains Proteins 0.000 description 10
- 241000283973 Oryctolagus cuniculus Species 0.000 description 10
- 230000003828 downregulation Effects 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 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
- 125000005647 linker group Chemical group 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 238000009739 binding Methods 0.000 description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000002679 microRNA Substances 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 108700011259 MicroRNAs Proteins 0.000 description 6
- 241000283984 Rodentia Species 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 210000003205 muscle Anatomy 0.000 description 6
- 241000271566 Aves Species 0.000 description 5
- 108010029485 Protein Isoforms Proteins 0.000 description 5
- 102000001708 Protein Isoforms Human genes 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 108091070501 miRNA Proteins 0.000 description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
- 239000002777 nucleoside Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 230000002861 ventricular Effects 0.000 description 5
- ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 description 4
- ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 206010020880 Hypertrophy Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 229940104302 cytosine Drugs 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 210000005240 left ventricle Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 210000002027 skeletal muscle Anatomy 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 3
- 229930024421 Adenine Natural products 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class 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 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229960000643 adenine Drugs 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical class O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001939 inductive effect Effects 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
- 210000004699 muscle spindle Anatomy 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 102200137849 rs371898076 Human genes 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 2
- RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 description 2
- PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 2
- HCGHYQLFMPXSDU-UHFFFAOYSA-N 7-methyladenine Chemical compound C1=NC(N)=C2N(C)C=NC2=N1 HCGHYQLFMPXSDU-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000003293 cardioprotective effect Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical group C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000001419 dependent effect Effects 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
- 239000000835 fiber Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 108091008709 muscle spindles Proteins 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000002510 pyrogen Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 239000002342 ribonucleoside Substances 0.000 description 2
- 210000005241 right ventricle Anatomy 0.000 description 2
- 239000011435 rock Substances 0.000 description 2
- 102200136804 rs121913624 Human genes 0.000 description 2
- 102200137647 rs121913625 Human genes 0.000 description 2
- 102200137864 rs121913637 Human genes 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002363 skeletal muscle cell Anatomy 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 229940113082 thymine Drugs 0.000 description 2
- 239000005495 thyroid hormone Substances 0.000 description 2
- 229940036555 thyroid hormone Drugs 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- YIMATHOGWXZHFX-WCTZXXKLSA-N (2r,3r,4r,5r)-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolane-2,4-diol Chemical compound COCCO[C@H]1[C@H](O)O[C@H](CO)[C@H]1O YIMATHOGWXZHFX-WCTZXXKLSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 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
- UHUHBFMZVCOEOV-UHFFFAOYSA-N 1h-imidazo[4,5-c]pyridin-4-amine Chemical compound NC1=NC=CC2=C1N=CN2 UHUHBFMZVCOEOV-UHFFFAOYSA-N 0.000 description 1
- WKMPTBDYDNUJLF-UHFFFAOYSA-N 2-fluoroadenine Chemical compound NC1=NC(F)=NC2=C1N=CN2 WKMPTBDYDNUJLF-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- PJWBTAIPBFWVHX-FJGDRVTGSA-N 4-amino-1-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@](F)(O)[C@H](O)[C@@H](CO)O1 PJWBTAIPBFWVHX-FJGDRVTGSA-N 0.000 description 1
- LUCHPKXVUGJYGU-XLPZGREQSA-N 5-methyl-2'-deoxycytidine Chemical class O=C1N=C(N)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 LUCHPKXVUGJYGU-XLPZGREQSA-N 0.000 description 1
- ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 description 1
- UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 description 1
- KXBCLNRMQPRVTP-UHFFFAOYSA-N 6-amino-1,5-dihydroimidazo[4,5-c]pyridin-4-one Chemical compound O=C1NC(N)=CC2=C1N=CN2 KXBCLNRMQPRVTP-UHFFFAOYSA-N 0.000 description 1
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 1
- LOSIULRWFAEMFL-UHFFFAOYSA-N 7-deazaguanine Chemical compound O=C1NC(N)=NC2=C1CC=N2 LOSIULRWFAEMFL-UHFFFAOYSA-N 0.000 description 1
- HRYKDUPGBWLLHO-UHFFFAOYSA-N 8-azaadenine Chemical compound NC1=NC=NC2=NNN=C12 HRYKDUPGBWLLHO-UHFFFAOYSA-N 0.000 description 1
- LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 description 1
- 229960005508 8-azaguanine Drugs 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 1
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 description 1
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 description 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
- 101000909256 Caldicellulosiruptor bescii (strain ATCC BAA-1888 / DSM 6725 / Z-1320) DNA polymerase I Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108010051609 Cardiac Myosins Proteins 0.000 description 1
- 102000013602 Cardiac Myosins Human genes 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 102000002585 Contractile Proteins Human genes 0.000 description 1
- 108010068426 Contractile Proteins Proteins 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 1
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000001039 Dystrophin Human genes 0.000 description 1
- 108010069091 Dystrophin Proteins 0.000 description 1
- 102220502827 Ephrin type-A receptor 3_K207N_mutation Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000287828 Gallus gallus 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
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108091027874 Group I catalytic intron Proteins 0.000 description 1
- 108091029499 Group II intron Proteins 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000588964 Homo sapiens Myosin-14 Proteins 0.000 description 1
- 101000588966 Homo sapiens Myosin-15 Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100025408 Mus musculus Myh7b gene Proteins 0.000 description 1
- 208000021908 Myocardial disease Diseases 0.000 description 1
- 102100026925 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Human genes 0.000 description 1
- 102100032973 Myosin-15 Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000282579 Pan Species 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
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 101000902592 Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1) DNA polymerase Proteins 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 102000004167 Ribonuclease P Human genes 0.000 description 1
- 108090000621 Ribonuclease P Proteins 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 241000251131 Sphyrna Species 0.000 description 1
- 206010049418 Sudden Cardiac Death Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- SHGAZHPCJJPHSC-NWVFGJFESA-N Tretinoin Chemical compound OC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NWVFGJFESA-N 0.000 description 1
- 101000987816 Triticum aestivum 16.9 kDa class I heat shock protein 1 Proteins 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000005083 alkoxyalkoxy group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 102000013640 alpha-Crystallin B Chain Human genes 0.000 description 1
- 108010051585 alpha-Crystallin B Chain Proteins 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002769 anti-restenotic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit 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
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 230000001756 cardiomyopathic effect Effects 0.000 description 1
- 230000008209 cardiovascular development Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 230000021040 cytoplasmic transport Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000035487 diastolic blood pressure Effects 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
- 239000003085 diluting agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 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
- 229960004887 ferric hydroxide Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000004108 freeze drying Methods 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
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940028435 intralipid Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 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
- 238000001638 lipofection Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 108010065781 myosin light chain 2 Proteins 0.000 description 1
- 210000001087 myotubule Anatomy 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 125000003835 nucleoside group Chemical group 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
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 102200137629 rs121913626 Human genes 0.000 description 1
- 102200137879 rs121913630 Human genes 0.000 description 1
- 102200137669 rs121913631 Human genes 0.000 description 1
- 102200137776 rs121913632 Human genes 0.000 description 1
- 102200136840 rs121913633 Human genes 0.000 description 1
- 102200137805 rs121913634 Human genes 0.000 description 1
- 102200137811 rs121913634 Human genes 0.000 description 1
- 102200137761 rs267606908 Human genes 0.000 description 1
- 102200137782 rs727503261 Human genes 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000000527 sonication 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
- 230000009870 specific binding Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000008719 thickening Effects 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
- 150000003573 thiols Chemical class 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229940075420 xanthine Drugs 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
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- 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
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—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
- C12N2310/321—2'-O-R Modification
-
- 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
- C12N2310/322—2'-R Modification
-
- 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
- C12N2310/33—Chemical structure of the base
- C12N2310/334—Modified C
- C12N2310/3341—5-Methylcytosine
-
- 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
- C12N2310/341—Gapmers, i.e. of the type ===---===
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
- C12N2310/3521—Methyl
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Cardiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462033018P | 2014-08-04 | 2014-08-04 | |
| US62/033,018 | 2014-08-04 | ||
| PCT/US2015/043571 WO2016022536A2 (en) | 2014-08-04 | 2015-08-04 | Inhibitors of myh7b and uses thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017528441A JP2017528441A (ja) | 2017-09-28 |
| JP2017528441A5 JP2017528441A5 (enExample) | 2019-12-05 |
| JP6637961B2 true JP6637961B2 (ja) | 2020-01-29 |
Family
ID=55179393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017506382A Expired - Fee Related JP6637961B2 (ja) | 2014-08-04 | 2015-08-04 | Ｍｙｈ７ｂの阻害剤およびその使用 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US9752144B2 (enExample) |
| EP (1) | EP3177327A4 (enExample) |
| JP (1) | JP6637961B2 (enExample) |
| KR (1) | KR20170042625A (enExample) |
| CN (1) | CN108064175A (enExample) |
| AR (1) | AR101449A1 (enExample) |
| AU (1) | AU2015301221B2 (enExample) |
| CA (1) | CA2957618A1 (enExample) |
| MX (1) | MX2017001674A (enExample) |
| TW (1) | TW201614069A (enExample) |
| WO (1) | WO2016022536A2 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW201614069A (en) | 2014-08-04 | 2016-04-16 | Miragen Therapeutics Inc | Inhibitors of MYH7B and uses thereof |
| US11198874B2 (en) * | 2014-08-20 | 2021-12-14 | Lifesplice Pharma Llc | SCN8A splice modulating oligonucleotides and methods of use thereof |
| US11015196B2 (en) | 2016-05-20 | 2021-05-25 | The General Hospital Corporation | Using microRNAs to control activation status of hepatic stellate cells and to prevent fibrosis in progressive liver diseases |
| 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 |
| US20190185816A1 (en) * | 2017-12-19 | 2019-06-20 | The Regents Of The University Of Michigan | Cardiac microtissue and uses thereof |
| EP3813844A1 (en) * | 2018-06-28 | 2021-05-05 | United Kingdom Research and Innovation | Treatment of cardiomyopathy through modulation of hypoxia-induced erna activity |
| WO2020028842A1 (en) * | 2018-08-02 | 2020-02-06 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating hypertrophic cardiomyopathy |
| US12018087B2 (en) | 2018-08-02 | 2024-06-25 | Dyne Therapeutics, Inc. | Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of delivering oligonucleotide to a subject |
| SG11202100928QA (en) | 2018-08-02 | 2021-02-25 | Dyne Therapeutics Inc | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| US11638761B2 (en) | 2021-07-09 | 2023-05-02 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating Facioscapulohumeral muscular dystrophy |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5270163A (en) | 1990-06-11 | 1993-12-14 | University Research Corporation | Methods for identifying nucleic acid ligands |
| US7517644B1 (en) * | 1991-08-23 | 2009-04-14 | Larry J. Smith | Method and compositions for cellular reprogramming |
| US5981505A (en) | 1993-01-26 | 1999-11-09 | The Trustees Of The University Of Pennsylvania | Compositions and methods for delivery of genetic material |
| AU7404994A (en) | 1993-07-30 | 1995-02-28 | Regents Of The University Of California, The | 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 |
| US6639062B2 (en) * | 1997-02-14 | 2003-10-28 | Isis Pharmaceuticals, Inc. | Aminooxy-modified nucleosidic compounds and oligomeric compounds prepared therefrom |
| 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 |
| JP2002510319A (ja) | 1997-07-01 | 2002-04-02 | アイシス・ファーマシューティカルス・インコーポレーテッド | オリゴヌクレオチドの消化管を介したデリバリーのための組成物及び方法 |
| 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 |
| US6838283B2 (en) | 1998-09-29 | 2005-01-04 | Isis Pharmaceuticals Inc. | Antisense modulation of survivin expression |
| US6716242B1 (en) | 1999-10-13 | 2004-04-06 | Peter A. Altman | Pulmonary vein stent and method for use |
| US6693187B1 (en) | 2000-10-17 | 2004-02-17 | Lievre Cornu Llc | Phosphinoamidite carboxlates and analogs thereof in the synthesis of oligonucleotides having reduced internucleotide charge |
| US7083642B2 (en) | 2000-12-22 | 2006-08-01 | Avantec Vascular Corporation | Delivery of therapeutic capable agents |
| US7247313B2 (en) | 2001-06-27 | 2007-07-24 | Advanced Cardiovascular Systems, Inc. | Polyacrylates coatings for implantable medical devices |
| US6589286B1 (en) | 2001-09-12 | 2003-07-08 | Jason Litner | Eustachian tube stent |
| US7236821B2 (en) | 2002-02-19 | 2007-06-26 | Cardiac Pacemakers, Inc. | Chronically-implanted device for sensing and therapy |
| JP4868739B2 (ja) | 2002-05-06 | 2012-02-01 | アルナイラム ファーマシューティカルズ， インコーポレイテッド | 核酸の送達法 |
| US20040133270A1 (en) | 2002-07-08 | 2004-07-08 | Axel Grandt | Drug eluting stent and methods of manufacture |
| US7294329B1 (en) | 2002-07-18 | 2007-11-13 | Advanced Cardiovascular Systems, Inc. | Poly(vinyl acetal) coatings for implantable medical devices |
| US7232573B1 (en) | 2002-09-26 | 2007-06-19 | Advanced Cardiovascular Systems, Inc. | Stent coatings containing self-assembled monolayers |
| US7087263B2 (en) | 2002-10-09 | 2006-08-08 | Advanced Cardiovascular Systems, Inc. | Rare limiting barriers for implantable medical devices |
| US7144422B1 (en) | 2002-11-13 | 2006-12-05 | Advanced Cardiovascular Systems, Inc. | Drug-eluting stent and methods of making the same |
| JP2006507841A (ja) * | 2002-11-14 | 2006-03-09 | ダーマコン， インコーポレイテッド | 機能的ｓｉＲＮＡおよび超機能的ｓｉＲＮＡ |
| US7105018B1 (en) | 2002-12-30 | 2006-09-12 | Advanced Cardiovascular Systems, Inc. | Drug-eluting stent cover and method of use |
| US7156869B1 (en) | 2003-01-27 | 2007-01-02 | Advanced Cardiovascular Systems, Inc. | Drug-eluting stent and delivery system with tapered stent in shoulder region |
| US7041127B2 (en) | 2003-05-28 | 2006-05-09 | Ledergerber Walter J | Textured and drug eluting coronary artery stent |
| US7055237B2 (en) | 2003-09-29 | 2006-06-06 | Medtronic Vascular, Inc. | Method of forming a drug eluting stent |
| US7722596B2 (en) | 2004-02-26 | 2010-05-25 | Osprey Medical, Inc. | Regional cardiac tissue treatment |
| US20070203445A1 (en) | 2004-02-26 | 2007-08-30 | V-Kardia Pty Ltd | Isolating cardiac circulation |
| EP1735037B1 (en) | 2004-02-26 | 2015-05-20 | Osprey Medical Inc. | Isolating cardiac circulation |
| US7842800B2 (en) * | 2004-04-02 | 2010-11-30 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory bacterial and bacterial associated oligonucleotides and uses thereof |
| WO2006089340A2 (en) | 2005-02-23 | 2006-08-31 | V-Kardia Pty Ltd | Polynucleotide delivery to cardiac tissue |
| AU2006292524A1 (en) | 2005-09-15 | 2007-03-29 | Duke University | Focused libraries, functional profiling, laser selex and deselex |
| CA2889540A1 (en) | 2005-09-15 | 2007-03-22 | Marina Biotech, Inc. | Improvements in or relating to amphoteric liposomes |
| BRPI0719995A2 (pt) * | 2006-12-14 | 2014-03-18 | Novartis Ag | Composições e métodos para tratar distúrbios musculares & cardiovasculares |
| AU2008283794B2 (en) * | 2007-07-31 | 2014-03-20 | Board Of Regents, The University Of Texas System | Micro-RNAs that control myosin expression and myofiber identity |
| ES2406686T3 (es) * | 2007-10-04 | 2013-06-07 | Santaris Pharma A/S | Micromirs |
| NZ594365A (en) * | 2009-02-04 | 2013-03-28 | Univ Texas | Dual targeting of miR-208a or miR-208b and miR-499 in the treatment of cardiac disorders or musculoskeletal disorders |
| EP3028707A1 (en) * | 2009-05-01 | 2016-06-08 | Ophthotech Corporation | Methods for treating or preventing ophthalmological diseases |
| US9297007B2 (en) * | 2010-05-28 | 2016-03-29 | Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patientenzorg | miRNAs involved in the blood brain barrier function |
| EP2652151A2 (en) * | 2010-12-15 | 2013-10-23 | Miragen Therapeutics | Microrna inhibitors comprising locked nucleotides |
| WO2012140234A1 (en) | 2011-04-13 | 2012-10-18 | Vib Vzw | Modulation of mirna in diseases with aberrant angiogenesis |
| WO2013043817A1 (en) * | 2011-09-20 | 2013-03-28 | Isis Phamaceuticals, Inc. | Antisense modulation of gcgr expression |
| KR20140091688A (ko) * | 2011-10-06 | 2014-07-22 | 미라젠 세러퓨틱스 인코포레이티드 | 마이크로rna 조절에 의한 전신 에너지 항상성의 제어 |
| CN107083385A (zh) * | 2012-04-20 | 2017-08-22 | 艾珀特玛治疗公司 | 产热的miRNA调节剂 |
| US9034839B2 (en) | 2012-04-20 | 2015-05-19 | Aptamir Therapeutics, Inc. | miRNA modulators of thermogenesis |
| US20150133529A1 (en) * | 2012-05-16 | 2015-05-14 | Rana Therapeutics, Inc. | Compositions and methods for modulating bdnf expression |
| HK1209781A1 (en) * | 2012-06-21 | 2016-04-08 | MiRagen Therapeutics, Inc. | Oligonucleotide-based inhibitors comprising locked nucleic acid motif |
| US9163235B2 (en) | 2012-06-21 | 2015-10-20 | MiRagen Therapeutics, Inc. | Inhibitors of the miR-15 family of micro-RNAs |
| TW201614069A (en) | 2014-08-04 | 2016-04-16 | Miragen Therapeutics Inc | Inhibitors of MYH7B and uses thereof |
-
2015
- 2015-08-04 TW TW104125326A patent/TW201614069A/zh unknown
- 2015-08-04 EP EP15829559.2A patent/EP3177327A4/en not_active Withdrawn
- 2015-08-04 WO PCT/US2015/043571 patent/WO2016022536A2/en not_active Ceased
- 2015-08-04 JP JP2017506382A patent/JP6637961B2/ja not_active Expired - Fee Related
- 2015-08-04 US US14/818,144 patent/US9752144B2/en not_active Expired - Fee Related
- 2015-08-04 KR KR1020177005777A patent/KR20170042625A/ko not_active Withdrawn
- 2015-08-04 MX MX2017001674A patent/MX2017001674A/es unknown
- 2015-08-04 CN CN201580052358.1A patent/CN108064175A/zh active Pending
- 2015-08-04 AR ARP150102501A patent/AR101449A1/es unknown
- 2015-08-04 CA CA2957618A patent/CA2957618A1/en not_active Abandoned
- 2015-08-04 AU AU2015301221A patent/AU2015301221B2/en not_active Ceased
-
2017
- 2017-08-24 US US15/685,983 patent/US10144930B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| TW201614069A (en) | 2016-04-16 |
| CA2957618A1 (en) | 2016-02-11 |
| CN108064175A (zh) | 2018-05-22 |
| JP2017528441A (ja) | 2017-09-28 |
| WO2016022536A2 (en) | 2016-02-11 |
| KR20170042625A (ko) | 2017-04-19 |
| WO2016022536A3 (en) | 2016-03-31 |
| EP3177327A2 (en) | 2017-06-14 |
| EP3177327A4 (en) | 2018-03-14 |
| US9752144B2 (en) | 2017-09-05 |
| AR101449A1 (es) | 2016-12-21 |
| MX2017001674A (es) | 2017-08-10 |
| AU2015301221B2 (en) | 2020-07-02 |
| US20160032286A1 (en) | 2016-02-04 |
| US10144930B2 (en) | 2018-12-04 |
| US20180094262A1 (en) | 2018-04-05 |
| AU2015301221A1 (en) | 2017-03-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6637961B2 (ja) | Ｍｙｈ７ｂの阻害剤およびその使用 | |
| JP5943608B2 (ja) | 心臓障害の治療におけるｍｉｒ−２０８およびｍｉｒ−４９９の二重ターゲティング | |
| US8871731B2 (en) | Micro-RNA for the regulation of cardiac apoptosis and contractile function | |
| CN103038349B (zh) | 调节通过miR-378实现的代谢 | |
| WO2010120969A1 (en) | Targeting of the mir-30 family and let-7 family as a treatment for heart disease | |
| CN113166760A (zh) | 用于抑制angptl8的新型rna组合物和方法 | |
| JP2018503646A (ja) | ｍｉＲ−９２阻害剤およびその使用 | |
| US20230365967A1 (en) | Abcd1 for treatment of neurodisorders | |
| JP6430945B2 (ja) | Ｒｎａ活性及び血管透過性の調節 | |
| WO2010129950A1 (en) | Micro-rna that regulates cardiac remodeling | |
| WO2018183127A1 (en) | Mir-92 inhibitors for treatment of heart failure | |
| PT1966368E (pt) | Inibição do igf-1r mediada por arni para o tratamento da angiogénese ocular |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180803 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190523 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190823 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20191023 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20191217 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20191223 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6637961 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |