CN102743767A - RNAi介导的Gremlin抑制用于治疗眼内压相关的状况 - Google Patents
RNAi介导的Gremlin抑制用于治疗眼内压相关的状况 Download PDFInfo
- Publication number
- CN102743767A CN102743767A CN2012102535702A CN201210253570A CN102743767A CN 102743767 A CN102743767 A CN 102743767A CN 2012102535702 A CN2012102535702 A CN 2012102535702A CN 201210253570 A CN201210253570 A CN 201210253570A CN 102743767 A CN102743767 A CN 102743767A
- Authority
- CN
- China
- Prior art keywords
- rna molecule
- seq
- nucleotide
- disturbance rna
- mrna
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102100038367 Gremlin-1 Human genes 0.000 title claims abstract description 80
- 101001032872 Homo sapiens Gremlin-1 Proteins 0.000 title claims abstract description 80
- 230000005764 inhibitory process Effects 0.000 title abstract description 5
- 108091030071 RNAI Proteins 0.000 title 1
- 230000001404 mediated effect Effects 0.000 title 1
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 22
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 218
- 239000002773 nucleotide Substances 0.000 claims description 114
- 125000003729 nucleotide group Chemical group 0.000 claims description 114
- 108020004999 messenger RNA Proteins 0.000 claims description 107
- 108020004459 Small interfering RNA Proteins 0.000 claims description 89
- 230000014509 gene expression Effects 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 38
- 230000000692 anti-sense effect Effects 0.000 claims description 34
- 230000000295 complement effect Effects 0.000 claims description 30
- 210000001508 eye Anatomy 0.000 claims description 28
- 108091027967 Small hairpin RNA Proteins 0.000 claims description 20
- 239000004055 small Interfering RNA Substances 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 19
- 108091081021 Sense strand Proteins 0.000 claims description 17
- 239000013604 expression vector Substances 0.000 claims description 14
- 230000004048 modification Effects 0.000 claims description 11
- 238000012986 modification Methods 0.000 claims description 11
- 238000001727 in vivo Methods 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 210000003786 sclera Anatomy 0.000 claims description 8
- 210000000795 conjunctiva Anatomy 0.000 claims description 6
- 108091070501 miRNA Proteins 0.000 claims description 6
- 210000001525 retina Anatomy 0.000 claims description 6
- 238000013459 approach Methods 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 239000000443 aerosol Substances 0.000 claims description 4
- 210000002159 anterior chamber Anatomy 0.000 claims description 4
- 238000007918 intramuscular administration Methods 0.000 claims description 4
- 238000007912 intraperitoneal administration Methods 0.000 claims description 4
- 238000001990 intravenous administration Methods 0.000 claims description 4
- 238000007920 subcutaneous administration Methods 0.000 claims description 4
- 210000005252 bulbus oculi Anatomy 0.000 claims description 3
- 238000011161 development Methods 0.000 claims description 3
- 210000003195 fascia Anatomy 0.000 claims description 3
- 210000005239 tubule Anatomy 0.000 claims description 3
- 210000004127 vitreous body Anatomy 0.000 claims description 3
- 239000002679 microRNA Substances 0.000 claims 2
- 239000002924 silencing RNA Substances 0.000 claims 2
- 230000004410 intraocular pressure Effects 0.000 abstract description 39
- 206010067013 Normal tension glaucoma Diseases 0.000 abstract description 7
- 206010030348 Open-Angle Glaucoma Diseases 0.000 abstract description 7
- 201000002978 low tension glaucoma Diseases 0.000 abstract description 7
- 206010030043 Ocular hypertension Diseases 0.000 abstract description 4
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 abstract 1
- 230000009368 gene silencing by RNA Effects 0.000 abstract 1
- 230000002452 interceptive effect Effects 0.000 description 134
- 210000004027 cell Anatomy 0.000 description 29
- 108090000623 proteins and genes Proteins 0.000 description 25
- 108020004414 DNA Proteins 0.000 description 18
- 238000009396 hybridization Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 12
- 230000008685 targeting Effects 0.000 description 12
- 238000001890 transfection Methods 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 238000013461 design Methods 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 108091034117 Oligonucleotide Proteins 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 8
- 102000039446 nucleic acids Human genes 0.000 description 8
- 150000007523 nucleic acids Chemical class 0.000 description 8
- 210000003733 optic disk Anatomy 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000008859 change Effects 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 210000003660 reticulum Anatomy 0.000 description 7
- -1 that is Proteins 0.000 description 7
- 239000013603 viral vector Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 6
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229940112869 bone morphogenetic protein Drugs 0.000 description 6
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 101710163270 Nuclease Proteins 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000003197 gene knockdown Methods 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 108091092562 ribozyme Proteins 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 230000000630 rising effect Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 108091028664 Ribonucleotide Proteins 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 210000001742 aqueous humor Anatomy 0.000 description 3
- 229960000686 benzalkonium chloride Drugs 0.000 description 3
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 210000004087 cornea Anatomy 0.000 description 3
- 239000005547 deoxyribonucleotide Substances 0.000 description 3
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000002105 nanoparticle Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000002336 ribonucleotide Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000012096 transfection reagent Substances 0.000 description 3
- 238000012384 transportation and delivery Methods 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 230000003313 weakening effect Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-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
- 229930024421 Adenine Natural products 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 2
- 102100040283 Peptidyl-prolyl cis-trans isomerase B Human genes 0.000 description 2
- 108091036066 Three prime untranslated region Proteins 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 229960000643 adenine Drugs 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
- 238000004458 analytical method Methods 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000002421 anti-septic effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000010668 complexation reaction Methods 0.000 description 2
- 108010048032 cyclophilin B Proteins 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000004438 eyesight Effects 0.000 description 2
- OUGPQMKVHOPOBY-UHFFFAOYSA-N gem 132 Chemical group COP(O)(=O)OCC1OC(N2C(NC(=O)C(C)=C2)=O)CC1OP(=O)(OC)OCC1OC(N2C3=C(C(NC(N)=N3)=O)N=C2)CC1OP(O)(=O)OCC1OC(N2C3=C(C(NC(N)=N3)=O)N=C2)CC1OP(O)(=O)OCC1OC(N2C3=C(C(NC(N)=N3)=O)N=C2)CC1OP(O)(=O)OCC1OC(N2C3=C(C(NC(N)=N3)=O)N=C2)CC1OP(O)(=O)OCC1OC(N2C(N=C(N)C=C2)=O)CC1OP(O)(=O)OCC1OC(N2C(NC(=O)C(C)=C2)=O)CC1OP(O)(=O)OCC1OC(N2C(NC(=O)C(C)=C2)=O)CC1OP(O)(=O)OCC1OC(N2C3=NC=NC(N)=C3N=C2)CC1OP(O)(=O)OCC1OC(N2C(N=C(N)C=C2)=O)CC1OP(O)(=O)OCC(C(C1)OP(O)(=O)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=O)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(=O)(OC)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(=O)(OC)OCC2C(CC(O2)N2C3=NC=NC(N)=C3N=C2)OP(=O)(OC)OCC2C(CC(O2)N2C3=NC=NC(N)=C3N=C2)OP(=O)(OC)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=O)OCC2C(CC(O2)N2C3=NC=NC(N)=C3N=C2)O)OC1N1C=CC(N)=NC1=O OUGPQMKVHOPOBY-UHFFFAOYSA-N 0.000 description 2
- 101150107752 grem1 gene Proteins 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 210000003458 notochord Anatomy 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 108010044156 peptidyl-prolyl cis-trans isomerase b Proteins 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000012385 systemic delivery Methods 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- LXAHHHIGZXPRKQ-UHFFFAOYSA-N 5-fluoro-2-methylpyridine Chemical compound CC1=CC=C(F)C=N1 LXAHHHIGZXPRKQ-UHFFFAOYSA-N 0.000 description 1
- XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical compound N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 description 1
- QZVTXIAWCGGNJA-UHFFFAOYSA-N 6-amino-8-methyl-7H-purine-2-sulfonic acid Chemical compound CC1=NC2=NC(=NC(=C2N1)N)S(=O)(=O)O QZVTXIAWCGGNJA-UHFFFAOYSA-N 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 101150019028 Antp gene Proteins 0.000 description 1
- 102000001893 Bone Morphogenetic Protein Receptors Human genes 0.000 description 1
- 108010040422 Bone Morphogenetic Protein Receptors Proteins 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 1
- 102100022526 Bone morphogenetic protein 5 Human genes 0.000 description 1
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 1
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000713730 Equine infectious anemia virus Species 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016970 Follistatin Human genes 0.000 description 1
- 108010014612 Follistatin Proteins 0.000 description 1
- 241000223783 Glaucoma Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 description 1
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 1
- 101000899388 Homo sapiens Bone morphogenetic protein 5 Proteins 0.000 description 1
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 description 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 101000611202 Homo sapiens Peptidyl-prolyl cis-trans isomerase B Proteins 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 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
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027417 Metabolic acidosis Diseases 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 101710149951 Protein Tat Proteins 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins 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
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- 101100137821 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PRP8 gene Proteins 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 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
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003260 anti-sepsis Effects 0.000 description 1
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229920006317 cationic polymer Polymers 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000036040 emmetropia Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010842 high-capacity cDNA reverse transcription kit Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 210000000554 iris Anatomy 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 210000000088 lip Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000005157 neural retina Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 229940100654 ophthalmic suspension Drugs 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 108010043655 penetratin Proteins 0.000 description 1
- MCYTYTUNNNZWOK-LCLOTLQISA-N penetratin Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 MCYTYTUNNNZWOK-LCLOTLQISA-N 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000003186 pharmaceutical solution Substances 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920000724 poly(L-arginine) polymer Polymers 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 201000006366 primary open angle glaucoma Diseases 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000004844 protein turnover Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000002213 purine nucleotide Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000003584 silencer Effects 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229930193551 sterin Natural products 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- SUEGWIXYCHISPX-UHFFFAOYSA-N sulfane trihydroxy(sulfanylidene)-lambda5-phosphane Chemical compound OP(O)(O)=S.S SUEGWIXYCHISPX-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 210000001745 uvea Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
Images
Classifications
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Ophthalmology & Optometry (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83982606P | 2006-08-24 | 2006-08-24 | |
| US60/839,826 | 2006-08-24 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800308171A Division CN101517081A (zh) | 2006-08-24 | 2007-08-24 | RNAi介导的Gremlin抑制用于治疗眼内压相关的状况 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102743767A true CN102743767A (zh) | 2012-10-24 |
Family
ID=39032079
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012102535702A Pending CN102743767A (zh) | 2006-08-24 | 2007-08-24 | RNAi介导的Gremlin抑制用于治疗眼内压相关的状况 |
| CNA2007800308171A Pending CN101517081A (zh) | 2006-08-24 | 2007-08-24 | RNAi介导的Gremlin抑制用于治疗眼内压相关的状况 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800308171A Pending CN101517081A (zh) | 2006-08-24 | 2007-08-24 | RNAi介导的Gremlin抑制用于治疗眼内压相关的状况 |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US20080051361A1 (enExample) |
| EP (1) | EP2059597A2 (enExample) |
| JP (1) | JP2010501188A (enExample) |
| KR (1) | KR20090042297A (enExample) |
| CN (2) | CN102743767A (enExample) |
| AU (1) | AU2007286545A1 (enExample) |
| BR (1) | BRPI0715821A2 (enExample) |
| CA (1) | CA2659464A1 (enExample) |
| MX (1) | MX2009001896A (enExample) |
| WO (1) | WO2008024983A2 (enExample) |
| ZA (1) | ZA200900553B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106978509A (zh) * | 2017-06-07 | 2017-07-25 | 中南大学湘雅二医院 | 青光眼诊断分子标记物lncRNAs ENST00000607393、试剂盒及应用 |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006006948A2 (en) * | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
| GB0708662D0 (en) * | 2007-05-04 | 2007-06-13 | Galapagos Nv | shRNA sequences |
| JP2010540564A (ja) * | 2007-10-01 | 2010-12-24 | アルコン リサーチ, リミテッド | 自己相補的なaavが媒介する眼の障害を処置または予防するための干渉rna分子の送達 |
| BRPI0802525A2 (pt) | 2008-07-11 | 2010-03-09 | Kiyoshi Hashiba | endoscópio cirúrgico |
| WO2010090762A1 (en) | 2009-02-04 | 2010-08-12 | Rxi Pharmaceuticals Corporation | Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
| EP2862929B1 (en) * | 2009-12-09 | 2017-09-06 | Quark Pharmaceuticals, Inc. | Compositions and methods for treating diseases, disorders or injury of the CNS |
| CN106074591B (zh) * | 2010-03-24 | 2020-01-14 | 菲奥医药公司 | 眼部症候中的rna干扰 |
| ES2899043T3 (es) | 2011-12-15 | 2022-03-09 | Bioneer Corp | Novedosos conjugados de oligonucleótidos y su uso |
| KR101722948B1 (ko) | 2012-01-05 | 2017-04-04 | (주)바이오니아 | 리간드가 결합된 이중나선 올리고 rna 구조체 및 그 제조방법 |
| CN104114704A (zh) | 2012-01-05 | 2014-10-22 | 株式会社百奥尼 | 高效率的纳米颗粒型双螺旋寡rna结构体及其制备方法 |
| EP2805713B1 (en) | 2012-01-18 | 2018-10-10 | Bioneer Corporation | Magnetic nanoparticle-samirna complex and method for preparing same |
| JP6339063B2 (ja) | 2012-03-15 | 2018-06-06 | エスエヌユー アールアンドディービー ファウンデーション | グレムリン−1に対する抗体 |
| GB201215857D0 (en) * | 2012-09-05 | 2012-10-24 | Sylentis Sau | siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions |
| EP2893018B1 (en) * | 2012-09-05 | 2019-07-24 | Sylentis S.A.U. | Sirna and their use in methods and compositions for the treatment and/or prevention of eye conditions |
| PL3018208T3 (pl) | 2013-07-05 | 2020-09-21 | Bioneer Corporation | Ulepszona struktura oligonukleotydowa typu nanocząstki o wysokiej wydajności i sposób jej wytwarzania |
| US10011837B2 (en) | 2014-03-04 | 2018-07-03 | Sylentis Sau | SiRNAs and their use in methods and compositions for the treatment and/or prevention of eye conditions |
| US11279934B2 (en) | 2014-04-28 | 2022-03-22 | Phio Pharmaceuticals Corp. | Methods for treating cancer using nucleic acids targeting MDM2 or MYCN |
| JP2017200928A (ja) * | 2017-05-31 | 2017-11-09 | シレンティス・エセ・ア・ウ | siRNAならびに眼の状態の処置および/または予防のための方法および組成物におけるその使用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100996226B1 (ko) * | 2001-10-31 | 2010-11-24 | 유니버시티 오브 노스 텍사스 헬스 사이언스 센터 | 뼈 형태발생 단백질(bmp), bmp 수용체 및 bmp결합 단백질 및 녹내장 진단 및 치료에서 그의 용도 |
| US20040138163A1 (en) * | 2002-05-29 | 2004-07-15 | Mcswiggen James | RNA interference mediated inhibition of vascular edothelial growth factor and vascular edothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| WO2006006948A2 (en) * | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
| US20060141049A1 (en) * | 2003-11-12 | 2006-06-29 | Allergan, Inc. | Triamcinolone compositions for intravitreal administration to treat ocular conditions |
| TW200639253A (en) * | 2005-02-01 | 2006-11-16 | Alcon Inc | RNAi-mediated inhibition of ocular targets |
-
2007
- 2007-08-24 BR BRPI0715821-1A patent/BRPI0715821A2/pt not_active IP Right Cessation
- 2007-08-24 CN CN2012102535702A patent/CN102743767A/zh active Pending
- 2007-08-24 CA CA002659464A patent/CA2659464A1/en not_active Abandoned
- 2007-08-24 AU AU2007286545A patent/AU2007286545A1/en not_active Abandoned
- 2007-08-24 WO PCT/US2007/076776 patent/WO2008024983A2/en not_active Ceased
- 2007-08-24 EP EP07841339A patent/EP2059597A2/en not_active Withdrawn
- 2007-08-24 ZA ZA200900553A patent/ZA200900553B/xx unknown
- 2007-08-24 US US11/844,869 patent/US20080051361A1/en not_active Abandoned
- 2007-08-24 JP JP2009525796A patent/JP2010501188A/ja active Pending
- 2007-08-24 KR KR1020097004684A patent/KR20090042297A/ko not_active Ceased
- 2007-08-24 CN CNA2007800308171A patent/CN101517081A/zh active Pending
- 2007-08-24 MX MX2009001896A patent/MX2009001896A/es active IP Right Grant
-
2010
- 2010-06-02 US US12/791,926 patent/US20100305193A1/en not_active Abandoned
-
2011
- 2011-10-26 US US13/281,785 patent/US20120077864A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106978509A (zh) * | 2017-06-07 | 2017-07-25 | 中南大学湘雅二医院 | 青光眼诊断分子标记物lncRNAs ENST00000607393、试剂盒及应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008024983A2 (en) | 2008-02-28 |
| CA2659464A1 (en) | 2008-02-28 |
| EP2059597A2 (en) | 2009-05-20 |
| US20100305193A1 (en) | 2010-12-02 |
| AU2007286545A1 (en) | 2008-02-28 |
| MX2009001896A (es) | 2009-04-17 |
| ZA200900553B (en) | 2010-04-28 |
| US20080051361A1 (en) | 2008-02-28 |
| CN101517081A (zh) | 2009-08-26 |
| BRPI0715821A2 (pt) | 2013-07-23 |
| US20120077864A1 (en) | 2012-03-29 |
| JP2010501188A (ja) | 2010-01-21 |
| KR20090042297A (ko) | 2009-04-29 |
| WO2008024983A3 (en) | 2008-10-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102743767A (zh) | RNAi介导的Gremlin抑制用于治疗眼内压相关的状况 | |
| US20220364097A1 (en) | RNAi-MEDIATED INHIBITION OF HIF1A FOR TREATMENT OF OCULAR ANGIOGENESIS | |
| CN101160138B (zh) | RNAi抑制CTGF用于治疗眼科疾病 | |
| CN101326285A (zh) | Rho激酶的RNAi介导的抑制用于治疗眼高压/青光眼 | |
| CN103285026A (zh) | 肿瘤坏死因子α相关状况的RNAi介导的抑制 | |
| US9422556B2 (en) | RNAi-related inhibition of TNF-alpha signaling pathway for treatment of ocular angiogenesis | |
| US9765340B2 (en) | RNAi-mediated inhibition of phosphodiesterase type 4 for treatment of CAMP-related ocular disorders | |
| US8865670B2 (en) | RNAi-related inhibition of TNFα signaling pathway for treatment of glaucoma | |
| US9173896B2 (en) | RNAi-mediated inhibition of connexin 43 for treatment of IOP-related conditions | |
| CN102172407A (zh) | 用于治疗青光眼的血清淀粉状蛋白A的RNAi抑制 | |
| ES2392185T3 (es) | Inhibición de IGF-1R mediada por ARNi para tratamiento de angiogénesis ocular | |
| CN101137754A (zh) | 用于治疗青光眼的卷曲相关蛋白-1的RNAi介导性抑制 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121024 |