CA2694091A1 - Self complementary aav-mediated delivery of interfering rna molecules to treat or prevent ocular disorders - Google Patents
Self complementary aav-mediated delivery of interfering rna molecules to treat or prevent ocular disorders Download PDFInfo
- Publication number
- CA2694091A1 CA2694091A1 CA2694091A CA2694091A CA2694091A1 CA 2694091 A1 CA2694091 A1 CA 2694091A1 CA 2694091 A CA2694091 A CA 2694091A CA 2694091 A CA2694091 A CA 2694091A CA 2694091 A1 CA2694091 A1 CA 2694091A1
- Authority
- CA
- Canada
- Prior art keywords
- interfering rna
- ocular
- scaav
- vector
- sirna
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000002452 interceptive effect Effects 0.000 title claims abstract description 100
- 208000022873 Ocular disease Diseases 0.000 title claims abstract description 28
- 238000012384 transportation and delivery Methods 0.000 title description 12
- 230000000295 complement effect Effects 0.000 title description 5
- 230000001404 mediated effect Effects 0.000 title description 4
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 42
- 230000014509 gene expression Effects 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 34
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 114
- 108020004459 Small interfering RNA Proteins 0.000 claims description 58
- 108020004999 messenger RNA Proteins 0.000 claims description 56
- 239000013609 scAAV vector Substances 0.000 claims description 31
- 239000013598 vector Substances 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 108091027967 Small hairpin RNA Proteins 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 208000010412 Glaucoma Diseases 0.000 claims description 11
- 238000002347 injection Methods 0.000 claims description 10
- 239000007924 injection Substances 0.000 claims description 10
- 230000033115 angiogenesis Effects 0.000 claims description 9
- 239000004055 small Interfering RNA Substances 0.000 claims description 9
- 241000702421 Dependoparvovirus Species 0.000 claims description 8
- 210000002845 virion Anatomy 0.000 claims description 8
- 206010030043 Ocular hypertension Diseases 0.000 claims description 6
- 230000004968 inflammatory condition Effects 0.000 claims description 6
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 5
- 206010013774 Dry eye Diseases 0.000 claims description 5
- 230000000699 topical effect Effects 0.000 claims description 5
- 239000002679 microRNA Substances 0.000 claims description 3
- 239000002924 silencing RNA Substances 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 2
- 239000007927 intramuscular injection Substances 0.000 claims description 2
- 239000007928 intraperitoneal injection Substances 0.000 claims description 2
- 238000010253 intravenous injection Methods 0.000 claims description 2
- 108091070501 miRNA Proteins 0.000 claims 2
- 239000013603 viral vector Substances 0.000 abstract description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 24
- 210000001508 eye Anatomy 0.000 description 23
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 17
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 17
- 239000002773 nucleotide Substances 0.000 description 16
- 125000003729 nucleotide group Chemical group 0.000 description 16
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 14
- 230000009368 gene silencing by RNA Effects 0.000 description 14
- 210000001585 trabecular meshwork Anatomy 0.000 description 14
- 238000003197 gene knockdown Methods 0.000 description 13
- 238000003776 cleavage reaction Methods 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 230000007017 scission Effects 0.000 description 10
- 230000000692 anti-sense effect Effects 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 230000008685 targeting Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 102000043279 ADAM17 Human genes 0.000 description 6
- 108091007505 ADAM17 Proteins 0.000 description 6
- 102000003945 NF-kappa B Human genes 0.000 description 6
- 108010057466 NF-kappa B Proteins 0.000 description 6
- 102100040283 Peptidyl-prolyl cis-trans isomerase B Human genes 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 108010048032 cyclophilin B Proteins 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 108010044156 peptidyl-prolyl cis-trans isomerase b Proteins 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 108700011259 MicroRNAs Proteins 0.000 description 4
- 206010029113 Neovascularisation Diseases 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- -1 cationic lipids Chemical class 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000004410 intraocular pressure Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 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 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
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 230000030279 gene silencing Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 210000001525 retina Anatomy 0.000 description 3
- 108010041788 rho-Associated Kinases Proteins 0.000 description 3
- 210000003786 sclera Anatomy 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 102100033639 Acetylcholinesterase Human genes 0.000 description 2
- 108010022752 Acetylcholinesterase Proteins 0.000 description 2
- 102100034608 Angiopoietin-2 Human genes 0.000 description 2
- 108010048036 Angiopoietin-2 Proteins 0.000 description 2
- 102000012002 Aquaporin 4 Human genes 0.000 description 2
- 108010036280 Aquaporin 4 Proteins 0.000 description 2
- 108050006947 CXC Chemokine Proteins 0.000 description 2
- 102000019388 CXC chemokine Human genes 0.000 description 2
- 102100033040 Carbonic anhydrase 12 Human genes 0.000 description 2
- 102100024633 Carbonic anhydrase 2 Human genes 0.000 description 2
- 101710167917 Carbonic anhydrase 2 Proteins 0.000 description 2
- 102100024644 Carbonic anhydrase 4 Human genes 0.000 description 2
- 101710167916 Carbonic anhydrase 4 Proteins 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 102000005600 Cathepsins Human genes 0.000 description 2
- 108010084457 Cathepsins Proteins 0.000 description 2
- 102100038731 Chitinase-3-like protein 2 Human genes 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 108010003101 ClC-3 channel Proteins 0.000 description 2
- 102000003712 Complement factor B Human genes 0.000 description 2
- 108090000056 Complement factor B Proteins 0.000 description 2
- 102000015225 Connective Tissue Growth Factor Human genes 0.000 description 2
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 description 2
- 108050001175 Connexin Proteins 0.000 description 2
- 102000010970 Connexin Human genes 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 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
- 102100038367 Gremlin-1 Human genes 0.000 description 2
- 102100034477 H(+)/Cl(-) exchange transporter 3 Human genes 0.000 description 2
- 101000883325 Homo sapiens Chitinase-3-like protein 2 Proteins 0.000 description 2
- 101001032872 Homo sapiens Gremlin-1 Proteins 0.000 description 2
- 101000861454 Homo sapiens Protein c-Fos Proteins 0.000 description 2
- 101000988419 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4D Proteins 0.000 description 2
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 101150008942 J gene Proteins 0.000 description 2
- 102100029839 Myocilin Human genes 0.000 description 2
- 101710196550 Myocilin Proteins 0.000 description 2
- 102000004070 NADPH Oxidase 4 Human genes 0.000 description 2
- 108010082699 NADPH Oxidase 4 Proteins 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 description 2
- 201000010183 Papilledema Diseases 0.000 description 2
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 2
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 102100027584 Protein c-Fos Human genes 0.000 description 2
- 102000004669 Protein-Lysine 6-Oxidase Human genes 0.000 description 2
- 108010003894 Protein-Lysine 6-Oxidase Proteins 0.000 description 2
- 208000002367 Retinal Perforations Diseases 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038886 Retinal oedema Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 2
- 102000004389 Ribonucleoproteins Human genes 0.000 description 2
- 108010081734 Ribonucleoproteins Proteins 0.000 description 2
- 102000054727 Serum Amyloid A Human genes 0.000 description 2
- 108700028909 Serum Amyloid A Proteins 0.000 description 2
- 102000008145 Sodium-Potassium-Chloride Symporters Human genes 0.000 description 2
- 108010074941 Sodium-Potassium-Chloride Symporters Proteins 0.000 description 2
- 108010016672 Syk Kinase Proteins 0.000 description 2
- 102100038183 Tyrosine-protein kinase SYK Human genes 0.000 description 2
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 229940022698 acetylcholinesterase Drugs 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 102100029170 cAMP-specific 3',5'-cyclic phosphodiesterase 4D Human genes 0.000 description 2
- 108010087312 carbonic anhydrase XII Proteins 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 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 2
- 210000004087 cornea Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000004406 elevated intraocular pressure Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 2
- 229940096397 interleukin-8 Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 201000003142 neovascular glaucoma Diseases 0.000 description 2
- 230000009437 off-target effect Effects 0.000 description 2
- 210000003733 optic disk Anatomy 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 230000004844 protein turnover Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 201000011195 retinal edema Diseases 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 208000032253 retinal ischemia Diseases 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012385 systemic delivery Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 239000012096 transfection reagent Substances 0.000 description 2
- 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
- KZMAWJRXKGLWGS-UHFFFAOYSA-N 2-chloro-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-n-(3-methoxypropyl)acetamide Chemical compound S1C(N(C(=O)CCl)CCCOC)=NC(C=2C=CC(OC)=CC=2)=C1 KZMAWJRXKGLWGS-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
- 108091006112 ATPases Proteins 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 101150019028 Antp gene Proteins 0.000 description 1
- 102000004888 Aquaporin 1 Human genes 0.000 description 1
- 108090001004 Aquaporin 1 Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 206010071321 Commotio retinae Diseases 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 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
- 102000053602 DNA Human genes 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 102000000543 Histamine Receptors Human genes 0.000 description 1
- 108010002059 Histamine Receptors Proteins 0.000 description 1
- 101000611202 Homo sapiens Peptidyl-prolyl cis-trans isomerase B Proteins 0.000 description 1
- 101001051767 Homo sapiens Protein kinase C beta type Proteins 0.000 description 1
- 101001041393 Homo sapiens Serine protease HTRA1 Proteins 0.000 description 1
- 101000693269 Homo sapiens Sphingosine 1-phosphate receptor 3 Proteins 0.000 description 1
- 101000763314 Homo sapiens Thrombomodulin Proteins 0.000 description 1
- 101000635958 Homo sapiens Transforming growth factor beta-2 proprotein Proteins 0.000 description 1
- 101000633069 Homo sapiens Transient receptor potential cation channel subfamily V member 1 Proteins 0.000 description 1
- 101000938391 Homo sapiens Transmembrane protein Proteins 0.000 description 1
- 101000818522 Homo sapiens fMet-Leu-Phe receptor Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 102000016878 Hypoxia-Inducible Factor 1 Human genes 0.000 description 1
- 108010028501 Hypoxia-Inducible Factor 1 Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000056430 Member 1 Solute Carrier Family 12 Human genes 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 101100286588 Mus musculus Igfl gene Proteins 0.000 description 1
- 102100021126 N-formyl peptide receptor 2 Human genes 0.000 description 1
- 101710091942 N-formyl peptide receptor 2 Proteins 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 102000012412 Presenilin-1 Human genes 0.000 description 1
- 108010036933 Presenilin-1 Proteins 0.000 description 1
- 101710149951 Protein Tat Proteins 0.000 description 1
- 102100024923 Protein kinase C beta type Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108010089507 Proto-Oncogene Proteins c-maf Proteins 0.000 description 1
- 102000007987 Proto-Oncogene Proteins c-maf Human genes 0.000 description 1
- 102000015176 Proton-Translocating ATPases Human genes 0.000 description 1
- 108010039518 Proton-Translocating ATPases Proteins 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 1
- 102000003661 Ribonuclease III Human genes 0.000 description 1
- 108010057163 Ribonuclease III 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
- 108091006621 SLC12A1 Proteins 0.000 description 1
- 102100030058 Secreted frizzled-related protein 1 Human genes 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 102100021119 Serine protease HTRA1 Human genes 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 102100025747 Sphingosine 1-phosphate receptor 3 Human genes 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 102100030737 Transforming growth factor beta-2 proprotein Human genes 0.000 description 1
- 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 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
- 241000700605 Viruses Species 0.000 description 1
- 108010020277 WD repeat containing planar cell polarity effector Proteins 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 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
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 description 1
- 230000003263 anti-adenoviral effect Effects 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 210000004240 ciliary body Anatomy 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 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
- 210000003717 douglas' pouch Anatomy 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 102100021145 fMet-Leu-Phe receptor Human genes 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000003633 gene expression assay Methods 0.000 description 1
- 230000037440 gene silencing effect Effects 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000000642 iatrogenic effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000000554 iris Anatomy 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 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
- 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
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940100655 ophthalmic gel Drugs 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 229940054534 ophthalmic solution 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
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 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
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 150000004713 phosphodiesters Chemical class 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
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 210000004777 protein coat Anatomy 0.000 description 1
- 238000000164 protein isolation Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000001590 sorbitan monolaureate Substances 0.000 description 1
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229940042596 viscoat Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- 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
- A61P27/04—Artificial tears; Irrigation solutions
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97655207P | 2007-10-01 | 2007-10-01 | |
| US60/976,552 | 2007-10-01 | ||
| PCT/US2008/078380 WO2009046059A1 (en) | 2007-10-01 | 2008-10-01 | Self complementary aav-mediated delivery of interfering rna molecules to treat or prevent ocular disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2694091A1 true CA2694091A1 (en) | 2009-04-09 |
Family
ID=40042637
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2694091A Abandoned CA2694091A1 (en) | 2007-10-01 | 2008-10-01 | Self complementary aav-mediated delivery of interfering rna molecules to treat or prevent ocular disorders |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20090087413A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2192926A1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2010540564A (cg-RX-API-DMAC7.html) |
| KR (1) | KR20100061792A (cg-RX-API-DMAC7.html) |
| CN (1) | CN101815536A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2008308784B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0817937A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2694091A1 (cg-RX-API-DMAC7.html) |
| MX (1) | MX2010001608A (cg-RX-API-DMAC7.html) |
| RU (1) | RU2010117178A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2009046059A1 (cg-RX-API-DMAC7.html) |
| ZA (1) | ZA201000423B (cg-RX-API-DMAC7.html) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2019143A1 (en) | 2007-07-23 | 2009-01-28 | Genethon | CNS gene delivery using peripheral administration of AAV vectors |
| EP2058401A1 (en) | 2007-10-05 | 2009-05-13 | Genethon | Widespread gene delivery to motor neurons using peripheral injection of AAV vectors |
| EP2287323A1 (en) | 2009-07-31 | 2011-02-23 | Association Institut de Myologie | Widespread gene delivery to the retina using systemic administration of AAV vectors |
| CN105821079B (zh) * | 2010-04-23 | 2021-10-26 | 佛罗里达大学研究基金公司 | 用于治疗莱伯氏先天性黑蒙-1(lca1)的raav-鸟苷酸环化酶组合物及方法 |
| CN103505743A (zh) | 2012-06-21 | 2014-01-15 | 北京命码生科科技有限公司 | 含功能性microRNA/siRNA的细胞微粒子及其应用 |
| EP4012035B1 (en) * | 2014-09-16 | 2024-11-06 | Genzyme Corporation | Adeno-associated viral vectors for treating myocilin (myoc) glaucoma |
| SG10201913430VA (en) * | 2014-09-16 | 2020-03-30 | Genzyme Corp | Adeno-associated viral vectors for treating myocilin (myoc) glaucoma |
| PL4012035T3 (pl) * | 2014-09-16 | 2025-03-24 | Genzyme Corporation | Wektory wirusowe związane z adenowirusami do leczenia jaskry miocylinowej (myoc) |
| GB201809588D0 (en) * | 2018-06-12 | 2018-07-25 | Univ Bristol | Materials and methods for modulating intraocular and intracranial pressure |
| KR20220076510A (ko) | 2019-10-08 | 2022-06-08 | 트러스티스 오브 보스톤 칼리지 | 다수의 서로 다른 비천연 아미노산을 함유하는 단백질 및 이러한 단백질의 제조 및 사용 방법 |
| JP2023517011A (ja) | 2020-03-05 | 2023-04-21 | ネオティーエックス セラピューティクス リミテッド | 免疫細胞を用いて癌を治療するための方法および組成物 |
| EP4161583A1 (en) * | 2020-06-05 | 2023-04-12 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods and pharmaceutical compositions for treating ocular diseases |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2505700T3 (es) * | 2000-06-01 | 2014-10-10 | University Of North Carolina At Chapel Hill | Vectores de parvovirus duplicados |
| US20040198682A1 (en) * | 2001-11-30 | 2004-10-07 | Mcswiggen James | RNA interference mediated inhibition of placental growth factor gene expression using short interfering nucleic acid (siNA) |
| US20050048529A1 (en) * | 2002-02-20 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
| US20040209832A1 (en) * | 2001-11-30 | 2004-10-21 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| NZ545544A (en) * | 2003-08-13 | 2009-04-30 | Univ Illinois | Silencing of TGF-beta receptor type II expression by sirna |
| WO2006042252A2 (en) * | 2004-10-08 | 2006-04-20 | Potentia Pharmeceuticals, Inc. | Viral complement control proteins for eye disorders |
| TWI386225B (zh) * | 2004-12-23 | 2013-02-21 | Alcon Inc | 用於治療眼睛病症的結締組織生長因子（ＣＴＧＦ）ＲＮＡ干擾（ＲＮＡｉ）抑制技術 |
| TWI401316B (zh) * | 2004-12-23 | 2013-07-11 | Alcon Inc | 用於治療青光眼之血清澱粉樣蛋白Ａ的ＲＮＡｉ抑制作用 |
| TW200639253A (en) * | 2005-02-01 | 2006-11-16 | Alcon Inc | RNAi-mediated inhibition of ocular targets |
| AU2006223131A1 (en) * | 2005-03-11 | 2006-09-21 | Alcon, Inc. | RNAi-mediated inhibition of frizzled related protein-1 for treatment of glaucoma |
| GB0521351D0 (en) * | 2005-10-20 | 2005-11-30 | Genomica Sau | Modulation of TRPV expression levels |
| AR057252A1 (es) * | 2005-12-27 | 2007-11-21 | Alcon Mfg Ltd | Inhibicion de rho quinasa mediada por arni para el tratamiento de trastornos oculares |
| TW200731980A (en) * | 2005-12-29 | 2007-09-01 | Alcon Mfg Ltd | RNAi-mediated inhibition of HIF1A for treatment of ocular angiogenesis |
| TW201336514A (zh) * | 2006-04-13 | 2013-09-16 | Alcon Res Ltd | ＲＮＡ干擾（ＲＮＡｉ）所媒介之與脾酪胺酸激酶相關之發炎症狀的抑制作用（二） |
| WO2007127428A2 (en) * | 2006-04-28 | 2007-11-08 | University Of Florida Research Foundation, Inc. | Double-stranded/self-complementary vectors with a truncated cba promoter and methods of gene delivery |
| CA2650416A1 (en) * | 2006-05-19 | 2007-11-29 | Alcon Research, Ltd. | Rnai-mediated inhibition of tumor necrosis factor .alpha.-related conditions |
| BRPI0715821A2 (pt) * | 2006-08-24 | 2013-07-23 | Alcon Res Ltd | inibiÇço de gremlina mediada por rnai para tratamento de condiÇÕes relacionadas À iop |
| EP2137205A2 (en) * | 2007-02-26 | 2009-12-30 | Quark Pharmaceuticals, Inc. | Inhibitors of rtp801 and their use in disease treatment |
| US7973019B1 (en) * | 2007-10-03 | 2011-07-05 | Alcon Research, Ltd. | Transferrin/transferrin receptor-mediated siRNA delivery |
| TW200932274A (en) * | 2007-12-18 | 2009-08-01 | Alcon Res Ltd | Interfering RNA delivery system and uses thereof |
-
2008
- 2008-10-01 WO PCT/US2008/078380 patent/WO2009046059A1/en not_active Ceased
- 2008-10-01 US US12/243,100 patent/US20090087413A1/en not_active Abandoned
- 2008-10-01 RU RU2010117178/15A patent/RU2010117178A/ru not_active Application Discontinuation
- 2008-10-01 MX MX2010001608A patent/MX2010001608A/es not_active Application Discontinuation
- 2008-10-01 AU AU2008308784A patent/AU2008308784B2/en not_active Ceased
- 2008-10-01 EP EP08835867A patent/EP2192926A1/en not_active Withdrawn
- 2008-10-01 BR BRPI0817937 patent/BRPI0817937A2/pt not_active IP Right Cessation
- 2008-10-01 CA CA2694091A patent/CA2694091A1/en not_active Abandoned
- 2008-10-01 JP JP2010527251A patent/JP2010540564A/ja active Pending
- 2008-10-01 KR KR1020107003620A patent/KR20100061792A/ko not_active Withdrawn
- 2008-10-01 CN CN200880110028A patent/CN101815536A/zh active Pending
-
2010
- 2010-01-20 ZA ZA2010/00423A patent/ZA201000423B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2008308784B2 (en) | 2013-07-18 |
| RU2010117178A (ru) | 2011-11-10 |
| EP2192926A1 (en) | 2010-06-09 |
| JP2010540564A (ja) | 2010-12-24 |
| AU2008308784A1 (en) | 2009-04-09 |
| BRPI0817937A2 (pt) | 2015-04-07 |
| WO2009046059A1 (en) | 2009-04-09 |
| KR20100061792A (ko) | 2010-06-09 |
| US20090087413A1 (en) | 2009-04-02 |
| MX2010001608A (es) | 2010-03-15 |
| ZA201000423B (en) | 2011-03-30 |
| CN101815536A (zh) | 2010-08-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008308784B2 (en) | Self complementary AAV-mediated delivery of interfering RNA molecules to treat or prevent ocular disorders | |
| US10138483B2 (en) | Transferrin/transferrin receptor-mediated siRNA delivery | |
| US9526799B2 (en) | Low density lipoprotein receptor-mediated siRNA delivery | |
| US9795684B2 (en) | Interfering RNA delivery system and uses thereof | |
| US9932584B2 (en) | Interfering RNA delivery system and uses thereof | |
| US20080214486A1 (en) | RNAi-MEDIATED INHIBITION OF AQUAPORIN 4 FOR TREATMENT OF IOP-RELATED CONDITIONS | |
| WO2012161677A1 (en) | TRANSFERRIN/TRANSFERRIN RECEPTOR-MEDIATED siRNA DELIVERY | |
| HK1117873B (en) | Rnai-mediated inhibition of igf-1r for treatment of ocular angiogenesis | |
| HK1117873A1 (en) | Rnai-mediated inhibition of igf-1r for treatment of ocular angiogenesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20141001 |