CA3205596A1 - Protection of cells from alu-rna-induced degeneration and inhibitors for protecting cells - Google Patents
Protection of cells from alu-rna-induced degeneration and inhibitors for protecting cellsInfo
- Publication number
- CA3205596A1 CA3205596A1 CA3205596A CA3205596A CA3205596A1 CA 3205596 A1 CA3205596 A1 CA 3205596A1 CA 3205596 A CA3205596 A CA 3205596A CA 3205596 A CA3205596 A CA 3205596A CA 3205596 A1 CA3205596 A1 CA 3205596A1
- Authority
- CA
- Canada
- Prior art keywords
- myd88
- cell
- inhibitor
- rpe
- rna
- 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
- 239000003112 inhibitor Substances 0.000 title claims description 148
- 230000007850 degeneration Effects 0.000 title claims description 126
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims abstract description 70
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims abstract description 38
- 230000014509 gene expression Effects 0.000 claims abstract description 37
- 210000004027 cell Anatomy 0.000 claims description 235
- 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 claims description 190
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 claims description 189
- 102000003810 Interleukin-18 Human genes 0.000 claims description 104
- 108090000171 Interleukin-18 Proteins 0.000 claims description 103
- 238000000034 method Methods 0.000 claims description 99
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 73
- 239000007924 injection Substances 0.000 claims description 52
- 238000002347 injection Methods 0.000 claims description 52
- 208000008069 Geographic Atrophy Diseases 0.000 claims description 50
- 230000005764 inhibitory process Effects 0.000 claims description 30
- 208000002780 macular degeneration Diseases 0.000 claims description 30
- 108090000623 proteins and genes Proteins 0.000 claims description 29
- 239000002158 endotoxin Substances 0.000 claims description 24
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 22
- 101000852483 Homo sapiens Interleukin-1 receptor-associated kinase 1 Proteins 0.000 claims description 19
- 102100036342 Interleukin-1 receptor-associated kinase 1 Human genes 0.000 claims description 19
- 230000011664 signaling Effects 0.000 claims description 18
- 230000000694 effects Effects 0.000 claims description 16
- 102100023533 Interleukin-1 receptor-associated kinase 4 Human genes 0.000 claims description 15
- 230000026731 phosphorylation Effects 0.000 claims description 15
- 238000006366 phosphorylation reaction Methods 0.000 claims description 15
- 101000977771 Homo sapiens Interleukin-1 receptor-associated kinase 4 Proteins 0.000 claims description 14
- 230000003833 cell viability Effects 0.000 claims description 14
- 230000001684 chronic effect Effects 0.000 claims description 13
- 230000003472 neutralizing effect Effects 0.000 claims description 13
- 239000013612 plasmid Substances 0.000 claims description 13
- 230000001154 acute effect Effects 0.000 claims description 12
- 230000008859 change Effects 0.000 claims description 12
- 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 claims description 12
- 239000012634 fragment Substances 0.000 claims description 11
- 210000004127 vitreous body Anatomy 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 230000004936 stimulating effect Effects 0.000 claims description 9
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 9
- 230000027455 binding Effects 0.000 claims description 8
- 210000004748 cultured cell Anatomy 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 8
- 230000002207 retinal effect Effects 0.000 claims description 8
- 238000012360 testing method Methods 0.000 claims description 8
- 206010048396 Bone marrow transplant rejection Diseases 0.000 claims description 7
- 206010052779 Transplant rejections Diseases 0.000 claims description 7
- 239000012190 activator Substances 0.000 claims description 7
- 210000000056 organ Anatomy 0.000 claims description 7
- 230000000699 topical effect Effects 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 201000005569 Gout Diseases 0.000 claims description 5
- 210000002159 anterior chamber Anatomy 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 210000000981 epithelium Anatomy 0.000 claims description 5
- 239000003889 eye drop Substances 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 210000003786 sclera Anatomy 0.000 claims description 5
- 238000013268 sustained release Methods 0.000 claims description 5
- 239000012730 sustained-release form Substances 0.000 claims description 5
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 claims description 4
- 208000030507 AIDS Diseases 0.000 claims description 4
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 4
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims description 4
- 206010003267 Arthritis reactive Diseases 0.000 claims description 4
- 208000011594 Autoinflammatory disease Diseases 0.000 claims description 4
- 201000003274 CINCA syndrome Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 4
- 206010012442 Dermatitis contact Diseases 0.000 claims description 4
- 208000035690 Familial cold urticaria Diseases 0.000 claims description 4
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 4
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 claims description 4
- 208000010159 IgA glomerulonephritis Diseases 0.000 claims description 4
- 206010021263 IgA nephropathy Diseases 0.000 claims description 4
- 206010022489 Insulin Resistance Diseases 0.000 claims description 4
- 102000003777 Interleukin-1 beta Human genes 0.000 claims description 4
- 108090000193 Interleukin-1 beta Proteins 0.000 claims description 4
- 208000012659 Joint disease Diseases 0.000 claims description 4
- 206010024229 Leprosy Diseases 0.000 claims description 4
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 4
- 201000002795 Muckle-Wells syndrome Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 101150000187 PTGS2 gene Proteins 0.000 claims description 4
- 206010035664 Pneumonia Diseases 0.000 claims description 4
- 208000001676 Polyomavirus Infections Diseases 0.000 claims description 4
- 206010063897 Renal ischaemia Diseases 0.000 claims description 4
- 206010039710 Scleroderma Diseases 0.000 claims description 4
- 206010040047 Sepsis Diseases 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 4
- 101150043341 Socs3 gene Proteins 0.000 claims description 4
- 208000004732 Systemic Vasculitis Diseases 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 208000027418 Wounds and injury Diseases 0.000 claims description 4
- 206010000496 acne Diseases 0.000 claims description 4
- 201000009961 allergic asthma Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 238000007675 cardiac surgery Methods 0.000 claims description 4
- 208000010247 contact dermatitis Diseases 0.000 claims description 4
- 201000003278 cryoglobulinemia Diseases 0.000 claims description 4
- 206010064570 familial cold autoinflammatory syndrome Diseases 0.000 claims description 4
- 244000000013 helminth Species 0.000 claims description 4
- 230000002757 inflammatory effect Effects 0.000 claims description 4
- 208000014674 injury Diseases 0.000 claims description 4
- 206010023332 keratitis Diseases 0.000 claims description 4
- 208000017169 kidney disease Diseases 0.000 claims description 4
- 201000004792 malaria Diseases 0.000 claims description 4
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 238000006384 oligomerization reaction Methods 0.000 claims description 4
- 230000002980 postoperative effect Effects 0.000 claims description 4
- 208000002574 reactive arthritis Diseases 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- 208000006379 syphilis Diseases 0.000 claims description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
- 208000037978 tubular injury Diseases 0.000 claims description 4
- 230000010024 tubular injury Effects 0.000 claims description 4
- 230000005747 tumor angiogenesis Effects 0.000 claims description 4
- 206010069657 Burkholderia cepacia complex infection Diseases 0.000 claims description 3
- 101150071146 COX2 gene Proteins 0.000 claims description 3
- 101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 claims description 3
- 102000004557 Interleukin-18 Receptors Human genes 0.000 claims description 3
- 108010017537 Interleukin-18 Receptors Proteins 0.000 claims description 3
- 241000725643 Respiratory syncytial virus Species 0.000 claims description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 3
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 3
- 108010070145 interleukin-18 binding protein Proteins 0.000 claims description 3
- 102000044166 interleukin-18 binding protein Human genes 0.000 claims description 3
- 208000017520 skin disease Diseases 0.000 claims description 3
- 230000004927 fusion Effects 0.000 claims description 2
- 239000007943 implant Substances 0.000 claims 4
- 230000015556 catabolic process Effects 0.000 claims 1
- 238000006731 degradation reaction Methods 0.000 claims 1
- 102000034287 fluorescent proteins Human genes 0.000 claims 1
- 108091006047 fluorescent proteins Proteins 0.000 claims 1
- 108090000426 Caspase-1 Proteins 0.000 abstract description 77
- 102100035904 Caspase-1 Human genes 0.000 abstract description 75
- 230000002401 inhibitory effect Effects 0.000 abstract description 70
- 102100022691 NACHT, LRR and PYD domains-containing protein 3 Human genes 0.000 abstract description 64
- 108010001946 Pyrin Domain-Containing 3 Protein NLR Family Proteins 0.000 abstract description 63
- 101000728679 Homo sapiens Apoptosis-associated speck-like protein containing a CARD Proteins 0.000 abstract description 49
- 102100029647 Apoptosis-associated speck-like protein containing a CARD Human genes 0.000 abstract description 48
- 239000002773 nucleotide Substances 0.000 abstract description 23
- 125000003729 nucleotide group Chemical group 0.000 abstract description 22
- 101001109465 Homo sapiens NACHT, LRR and PYD domains-containing protein 3 Proteins 0.000 abstract description 5
- 102000005583 Pyrin Human genes 0.000 abstract description 3
- 108010059278 Pyrin Proteins 0.000 abstract description 3
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 202
- 241000699670 Mus sp. Species 0.000 description 117
- 108090000765 processed proteins & peptides Proteins 0.000 description 81
- 108010034143 Inflammasomes Proteins 0.000 description 62
- 101000670189 Homo sapiens Ribulose-phosphate 3-epimerase Proteins 0.000 description 60
- 108020004459 Small interfering RNA Proteins 0.000 description 59
- 230000004913 activation Effects 0.000 description 53
- 102100023387 Endoribonuclease Dicer Human genes 0.000 description 51
- 239000004055 small Interfering RNA Substances 0.000 description 50
- 229920001184 polypeptide Polymers 0.000 description 49
- 102000004196 processed proteins & peptides Human genes 0.000 description 49
- 239000000203 mixture Substances 0.000 description 44
- 101000907904 Homo sapiens Endoribonuclease Dicer Proteins 0.000 description 42
- 241000699666 Mus <mouse, genus> Species 0.000 description 42
- 108010022133 Voltage-Dependent Anion Channel 1 Proteins 0.000 description 36
- 102000012290 Voltage-Dependent Anion Channel 1 Human genes 0.000 description 36
- 108091034117 Oligonucleotide Proteins 0.000 description 35
- 108010022109 Voltage-Dependent Anion Channel 2 Proteins 0.000 description 35
- 102000012249 Voltage-Dependent Anion Channel 2 Human genes 0.000 description 35
- 102000004091 Caspase-8 Human genes 0.000 description 33
- 108090000538 Caspase-8 Proteins 0.000 description 33
- 239000003642 reactive oxygen metabolite Substances 0.000 description 33
- 241000282414 Homo sapiens Species 0.000 description 32
- 239000013615 primer Substances 0.000 description 29
- 230000002441 reversible effect Effects 0.000 description 29
- 230000030833 cell death Effects 0.000 description 26
- 102000002689 Toll-like receptor Human genes 0.000 description 21
- 108020000411 Toll-like receptor Proteins 0.000 description 21
- 108091008099 NLRP3 inflammasome Proteins 0.000 description 20
- 238000003776 cleavage reaction Methods 0.000 description 19
- 230000007017 scission Effects 0.000 description 19
- 238000011282 treatment Methods 0.000 description 19
- 229940122390 Inflammasome inhibitor Drugs 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 231100000135 cytotoxicity Toxicity 0.000 description 16
- 230000003013 cytotoxicity Effects 0.000 description 16
- 238000012216 screening Methods 0.000 description 16
- 238000001262 western blot Methods 0.000 description 16
- -1 NFKB Proteins 0.000 description 15
- 230000000692 anti-sense effect Effects 0.000 description 15
- 239000002953 phosphate buffered saline Substances 0.000 description 14
- 239000013598 vector Substances 0.000 description 14
- 230000006870 function Effects 0.000 description 13
- 239000002679 microRNA Substances 0.000 description 13
- 230000002438 mitochondrial effect Effects 0.000 description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- 238000003384 imaging method Methods 0.000 description 12
- 101000850658 Homo sapiens Voltage-dependent anion-selective channel protein 3 Proteins 0.000 description 11
- 238000000692 Student's t-test Methods 0.000 description 11
- 150000001413 amino acids Chemical class 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 11
- 210000003470 mitochondria Anatomy 0.000 description 11
- 102000011727 Caspases Human genes 0.000 description 10
- 108010076667 Caspases Proteins 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 108090001129 Voltage-dependent anion channels Proteins 0.000 description 10
- 230000006735 deficit Effects 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 230000001404 mediated effect Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 102000008230 Toll-like receptor 3 Human genes 0.000 description 9
- 108010060885 Toll-like receptor 3 Proteins 0.000 description 9
- 102000004962 Voltage-dependent anion channels Human genes 0.000 description 9
- 230000002950 deficient Effects 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 210000002540 macrophage Anatomy 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 8
- 108700011259 MicroRNAs Proteins 0.000 description 8
- 102000003970 Vinculin Human genes 0.000 description 8
- 108090000384 Vinculin Proteins 0.000 description 8
- 102100033099 Voltage-dependent anion-selective channel protein 3 Human genes 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 239000003242 anti bacterial agent Substances 0.000 description 8
- 229940088710 antibiotic agent Drugs 0.000 description 8
- 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 8
- 210000002865 immune cell Anatomy 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 201000004569 Blindness Diseases 0.000 description 7
- 229940100513 Caspase 8 inhibitor Drugs 0.000 description 7
- 102000015696 Interleukins Human genes 0.000 description 7
- 108010063738 Interleukins Proteins 0.000 description 7
- 101150053046 MYD88 gene Proteins 0.000 description 7
- 238000009825 accumulation Methods 0.000 description 7
- 210000001185 bone marrow Anatomy 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 108091070501 miRNA Proteins 0.000 description 7
- 230000037452 priming Effects 0.000 description 7
- 108020004463 18S ribosomal RNA Proteins 0.000 description 6
- 239000004471 Glycine Substances 0.000 description 6
- 108010052550 MDL 201053 Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- OZLBDYMWFAHSOQ-UHFFFAOYSA-N diphenyliodanium Chemical compound C=1C=CC=CC=1[I+]C1=CC=CC=C1 OZLBDYMWFAHSOQ-UHFFFAOYSA-N 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 230000006010 pyroptosis Effects 0.000 description 6
- 238000003753 real-time PCR Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 108091032955 Bacterial small RNA Proteins 0.000 description 5
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 5
- 102100039340 Interleukin-18 receptor 1 Human genes 0.000 description 5
- 101710184759 Interleukin-18 receptor 1 Proteins 0.000 description 5
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 5
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 5
- 230000000975 bioactive effect Effects 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 210000003986 cell retinal photoreceptor Anatomy 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000035800 maturation Effects 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- PXEZTIWVRVSYOK-UHFFFAOYSA-N 2-(3,6-diacetyloxy-2,7-dichloro-9h-xanthen-9-yl)benzoic acid Chemical compound C1=2C=C(Cl)C(OC(=O)C)=CC=2OC2=CC(OC(C)=O)=C(Cl)C=C2C1C1=CC=CC=C1C(O)=O PXEZTIWVRVSYOK-UHFFFAOYSA-N 0.000 description 4
- 108091023043 Alu Element Proteins 0.000 description 4
- 102000003952 Caspase 3 Human genes 0.000 description 4
- 108090000397 Caspase 3 Proteins 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 101150089023 FASLG gene Proteins 0.000 description 4
- 102000004722 NADPH Oxidases Human genes 0.000 description 4
- 108010002998 NADPH Oxidases Proteins 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 108010038807 Oligopeptides Proteins 0.000 description 4
- 102000015636 Oligopeptides Human genes 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 239000000074 antisense oligonucleotide Substances 0.000 description 4
- 238000012230 antisense oligonucleotides Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 102000056368 human NLRP3 Human genes 0.000 description 4
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 4
- GVZFUVXPTPGOQT-UHFFFAOYSA-M mitoq Chemical compound CS([O-])(=O)=O.O=C1C(OC)=C(OC)C(=O)C(CCCCCCCCCC[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C GVZFUVXPTPGOQT-UHFFFAOYSA-M 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 102100037435 Antiviral innate immune response receptor RIG-I Human genes 0.000 description 3
- 101710127675 Antiviral innate immune response receptor RIG-I Proteins 0.000 description 3
- SJDDOCKBXFJEJB-MOKWFATOSA-N Belnacasan Chemical group CCO[C@@H]1OC(=O)C[C@@H]1NC(=O)[C@H]1N(C(=O)[C@@H](NC(=O)C=2C=C(Cl)C(N)=CC=2)C(C)(C)C)CCC1 SJDDOCKBXFJEJB-MOKWFATOSA-N 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 102000016911 Deoxyribonucleases Human genes 0.000 description 3
- 108010053770 Deoxyribonucleases Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 3
- 101000960954 Homo sapiens Interleukin-18 Proteins 0.000 description 3
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 3
- 101000805450 Homo sapiens Voltage-dependent anion-selective channel protein 1 Proteins 0.000 description 3
- 101000805418 Homo sapiens Voltage-dependent anion-selective channel protein 2 Proteins 0.000 description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 3
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 3
- 239000012097 Lipofectamine 2000 Substances 0.000 description 3
- 238000000585 Mann–Whitney U test Methods 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 101100079026 Mus musculus Myd88 gene Proteins 0.000 description 3
- 101100483777 Mus musculus Unc93b1 gene Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108091061750 Signal recognition particle RNA Proteins 0.000 description 3
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 3
- 102000044820 Zonula Occludens-1 Human genes 0.000 description 3
- 108700007340 Zonula Occludens-1 Proteins 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
- 239000005557 antagonist Substances 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 230000008436 biogenesis Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000006721 cell death pathway Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000006471 dimerization reaction Methods 0.000 description 3
- 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 3
- 230000005284 excitation Effects 0.000 description 3
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 3
- 102000050702 human PYCARD Human genes 0.000 description 3
- 102000050854 human VDAC1 Human genes 0.000 description 3
- 102000050892 human VDAC2 Human genes 0.000 description 3
- 102000056699 human VDAC3 Human genes 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 108010027775 interleukin-1beta-converting enzyme inhibitor Proteins 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- HPEUEJRPDGMIMY-IFQPEPLCSA-N molybdopterin Chemical compound O([C@H]1N2)[C@H](COP(O)(O)=O)C(S)=C(S)[C@@H]1NC1=C2N=C(N)NC1=O HPEUEJRPDGMIMY-IFQPEPLCSA-N 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 235000019419 proteases Nutrition 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 210000001525 retina Anatomy 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 3
- 230000004393 visual impairment Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- LPIARALSGDVZEP-SJVNDZIOSA-N (3s)-3-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-4-oxobutanoic acid Chemical compound OC(=O)C[C@@H](C=O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(C)=O)CC1=CC=C(O)C=C1 LPIARALSGDVZEP-SJVNDZIOSA-N 0.000 description 2
- UOUBHJRCKHLGFB-DGJUNBOTSA-N (3s)-3-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-5-chloro-4-oxopentanoic acid Chemical compound OC(=O)C[C@@H](C(=O)CCl)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(C)=O)CC1=CC=C(O)C=C1 UOUBHJRCKHLGFB-DGJUNBOTSA-N 0.000 description 2
- CXAGHAZMQSCAKJ-WAHHBDPQSA-N (4s,7s)-n-[(2r,3s)-2-ethoxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-6,10-dioxo-2,3,4,7,8,9-hexahydro-1h-pyridazino[1,2-a]diazepine-4-carboxamide Chemical compound CCO[C@@H]1OC(=O)C[C@@H]1NC(=O)[C@H]1N(C(=O)[C@H](CCC2=O)NC(=O)C=3C4=CC=CC=C4C=CN=3)N2CCC1 CXAGHAZMQSCAKJ-WAHHBDPQSA-N 0.000 description 2
- DOEWDSDBFRHVAP-KRXBUXKQSA-N (E)-3-tosylacrylonitrile Chemical compound CC1=CC=C(S(=O)(=O)\C=C\C#N)C=C1 DOEWDSDBFRHVAP-KRXBUXKQSA-N 0.000 description 2
- YSCNMFDFYJUPEF-OWOJBTEDSA-N 4,4'-diisothiocyano-trans-stilbene-2,2'-disulfonic acid Chemical compound OS(=O)(=O)C1=CC(N=C=S)=CC=C1\C=C\C1=CC=C(N=C=S)C=C1S(O)(=O)=O YSCNMFDFYJUPEF-OWOJBTEDSA-N 0.000 description 2
- UPXRTVAIJMUAQR-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)OC(C)(C)C)CC1NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 UPXRTVAIJMUAQR-UHFFFAOYSA-N 0.000 description 2
- 101710159080 Aconitate hydratase A Proteins 0.000 description 2
- 101710159078 Aconitate hydratase B Proteins 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- 108091023037 Aptamer Proteins 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 238000009010 Bradford assay Methods 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108010051219 Cre recombinase Proteins 0.000 description 2
- 101100117236 Drosophila melanogaster speck gene 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
- 101150023409 Eif2ak2 gene Proteins 0.000 description 2
- 102100026693 FAS-associated death domain protein Human genes 0.000 description 2
- 108010077716 Fas-Associated Death Domain Protein Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000715398 Homo sapiens Caspase-1 Proteins 0.000 description 2
- 101001109463 Homo sapiens NACHT, LRR and PYD domains-containing protein 1 Proteins 0.000 description 2
- 101000595548 Homo sapiens TIR domain-containing adapter molecule 1 Proteins 0.000 description 2
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 102100027353 Interferon-induced helicase C domain-containing protein 1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 108010072621 Interleukin-1 Receptor-Associated Kinases Proteins 0.000 description 2
- 102000006940 Interleukin-1 Receptor-Associated Kinases Human genes 0.000 description 2
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 2
- 238000000719 MTS assay Methods 0.000 description 2
- 231100000070 MTS assay Toxicity 0.000 description 2
- GNKNIPRNBZCJGO-UHFFFAOYSA-N Malyngamide F acetate Natural products CCCCCCCC(OC)CC=CCCC(=O)NCC(=CCl)C1=CCCC(OC(C)=O)C1=O GNKNIPRNBZCJGO-UHFFFAOYSA-N 0.000 description 2
- 108091028049 Mir-221 microRNA Proteins 0.000 description 2
- 102100023727 Mitochondrial antiviral-signaling protein Human genes 0.000 description 2
- 101710142315 Mitochondrial antiviral-signaling protein Proteins 0.000 description 2
- 101100273286 Mus musculus Casp4 gene Proteins 0.000 description 2
- 102100022698 NACHT, LRR and PYD domains-containing protein 1 Human genes 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 241000233805 Phoenix Species 0.000 description 2
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 2
- 241000053208 Porcellio laevis Species 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 2
- 101710105008 RNA-binding protein Proteins 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 241000191043 Rhodobacter sphaeroides Species 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100036073 TIR domain-containing adapter molecule 1 Human genes 0.000 description 2
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 2
- 238000002679 ablation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- ASXVEBPEZMSPHB-YJBOKZPZSA-N benzyl n-[(2s)-1-[[(2s)-4-fluoro-3-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)CF)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 ASXVEBPEZMSPHB-YJBOKZPZSA-N 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- SDZRWUKZFQQKKV-JHADDHBZSA-N cytochalasin D Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@H]\3[C@]2([C@@H](/C=C/[C@@](C)(O)C(=O)[C@@H](C)C/C=C/3)OC(C)=O)C(=O)N1)=C)C)C1=CC=CC=C1 SDZRWUKZFQQKKV-JHADDHBZSA-N 0.000 description 2
- 230000001120 cytoprotective effect Effects 0.000 description 2
- 238000000326 densiometry Methods 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 102000043959 human IL18 Human genes 0.000 description 2
- 102000055222 human IL1B Human genes 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 239000012133 immunoprecipitate Substances 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 108091005434 innate immune receptors Proteins 0.000 description 2
- 230000015788 innate immune response Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940047122 interleukins Drugs 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 229960004184 ketamine hydrochloride Drugs 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- NLZNSSWGRVBWIX-KRCBVYEFSA-N methyl (4s)-5-[[(2s)-1-[[(3s)-5-fluoro-1-methoxy-1,4-dioxopentan-3-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-[[(2s)-3-(1h-indol-3-yl)-2-(phenylmethoxycarbonylamino)propanoyl]amino]-5-oxopentanoate Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(=O)OC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(=O)OC)C(=O)CF)C(=O)OCC1=CC=CC=C1 NLZNSSWGRVBWIX-KRCBVYEFSA-N 0.000 description 2
- 108091061917 miR-221 stem-loop Proteins 0.000 description 2
- 108091063489 miR-221-1 stem-loop Proteins 0.000 description 2
- 108091055391 miR-221-2 stem-loop Proteins 0.000 description 2
- 108091031076 miR-221-3 stem-loop Proteins 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000011022 opal Substances 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000010399 physical interaction Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000000730 protein immunoprecipitation Methods 0.000 description 2
- 210000001747 pupil Anatomy 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000003146 transient transfection Methods 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229960004791 tropicamide Drugs 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 2
- 229960001600 xylazine Drugs 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- XZFMJVJDSYRWDQ-AWFVSMACSA-N (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid Chemical compound OC(=O)[C@]1(N)CN[C@@H](C(O)=O)C1 XZFMJVJDSYRWDQ-AWFVSMACSA-N 0.000 description 1
- XGWSRLSPWIEMLQ-RQLZCWDZSA-N (2S)-1-[(2S)-3-methyl-1-oxo-2-[[oxo-[(2S,3S)-3-[oxo(propylamino)methyl]-2-oxiranyl]methyl]amino]pentyl]-2-pyrrolidinecarboxylic acid methyl ester Chemical compound CCCNC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](C(C)CC)C(=O)N1[C@H](C(=O)OC)CCC1 XGWSRLSPWIEMLQ-RQLZCWDZSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-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
- AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 108091008098 AIM2 inflammasome Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 102100028100 Activating signal cointegrator 1 Human genes 0.000 description 1
- 101710089542 Activating signal cointegrator 1 Proteins 0.000 description 1
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 1
- 206010001258 Adenoviral infections Diseases 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102100022794 Bestrophin-1 Human genes 0.000 description 1
- 102100025752 CASP8 and FADD-like apoptosis regulator Human genes 0.000 description 1
- 101710100501 CASP8 and FADD-like apoptosis regulator Proteins 0.000 description 1
- 102000004066 Caspase-12 Human genes 0.000 description 1
- 108090000570 Caspase-12 Proteins 0.000 description 1
- 102100025597 Caspase-4 Human genes 0.000 description 1
- 101710090338 Caspase-4 Proteins 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108091008102 DNA aptamers Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 102000010170 Death domains Human genes 0.000 description 1
- 108050001718 Death domains Proteins 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010039471 Fas Ligand Protein Proteins 0.000 description 1
- 102100039928 Gamma-interferon-inducible protein 16 Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 238000010867 Hoechst staining Methods 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000903449 Homo sapiens Bestrophin-1 Proteins 0.000 description 1
- 101000960209 Homo sapiens Gamma-interferon-inducible protein 16 Proteins 0.000 description 1
- 101001082073 Homo sapiens Interferon-induced helicase C domain-containing protein 1 Proteins 0.000 description 1
- 101001033233 Homo sapiens Interleukin-10 Proteins 0.000 description 1
- 101001019591 Homo sapiens Interleukin-18-binding protein Proteins 0.000 description 1
- 101000979572 Homo sapiens NLR family CARD domain-containing protein 4 Proteins 0.000 description 1
- 101000962053 Homo sapiens Pyrin Proteins 0.000 description 1
- 101000608230 Homo sapiens Pyrin domain-containing protein 2 Proteins 0.000 description 1
- 241001502974 Human gammaherpesvirus 8 Species 0.000 description 1
- 101710128560 Initiator protein NS1 Proteins 0.000 description 1
- 102000002227 Interferon Type I Human genes 0.000 description 1
- 108010014726 Interferon Type I Proteins 0.000 description 1
- 101710085994 Interferon-induced helicase C domain-containing protein 1 Proteins 0.000 description 1
- 102100027355 Interferon-induced protein with tetratricopeptide repeats 1 Human genes 0.000 description 1
- 101710166699 Interferon-induced protein with tetratricopeptide repeats 1 Proteins 0.000 description 1
- 102100039065 Interleukin-1 beta Human genes 0.000 description 1
- 101710199010 Interleukin-1 receptor-associated kinase 4 Proteins 0.000 description 1
- 102100036433 Interleukin-1 receptor-associated kinase-like 2 Human genes 0.000 description 1
- 101710182491 Interleukin-1 receptor-associated kinase-like 2 Proteins 0.000 description 1
- 102100035017 Interleukin-18-binding protein Human genes 0.000 description 1
- 108010093442 L 709049 Proteins 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 231100000757 Microbial toxin Toxicity 0.000 description 1
- 108091028232 Mir-184 Proteins 0.000 description 1
- 101100233098 Mus musculus Ifngr1 gene Proteins 0.000 description 1
- 101000960949 Mus musculus Interleukin-18 Proteins 0.000 description 1
- 101100404869 Mus musculus Nlrp3 gene Proteins 0.000 description 1
- 229940123857 NADPH oxidase inhibitor Drugs 0.000 description 1
- 102000012064 NLR Proteins Human genes 0.000 description 1
- 108010036473 NLR Proteins Proteins 0.000 description 1
- 102100023435 NLR family CARD domain-containing protein 4 Human genes 0.000 description 1
- 101710144127 Non-structural protein 1 Proteins 0.000 description 1
- XVZUMQAMCYSUMS-SIUGBPQLSA-N OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 XVZUMQAMCYSUMS-SIUGBPQLSA-N 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- BUQLXKSONWUQAC-UHFFFAOYSA-N Parthenolide Natural products CC1C2OC(=O)C(=C)C2CCC(=C/CCC1(C)O)C BUQLXKSONWUQAC-UHFFFAOYSA-N 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 102100039891 Pyrin domain-containing protein 2 Human genes 0.000 description 1
- 108091008103 RNA aptamers Proteins 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 201000007737 Retinal degeneration Diseases 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 101710181913 Serine proteinase inhibitor 2 Proteins 0.000 description 1
- 108050000761 Serpin Proteins 0.000 description 1
- 102000008847 Serpin Human genes 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- YCUVUDODLRLVIC-UHFFFAOYSA-N Sudan black B Chemical compound C1=CC(=C23)NC(C)(C)NC2=CC=CC3=C1N=NC(C1=CC=CC=C11)=CC=C1N=NC1=CC=CC=C1 YCUVUDODLRLVIC-UHFFFAOYSA-N 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 1
- 102100038836 Superoxide dismutase [Cu-Zn] Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 1
- 108091026822 U6 spliceosomal RNA Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- MIFGOLAMNLSLGH-QOKNQOGYSA-N Z-Val-Ala-Asp(OMe)-CH2F Chemical compound COC(=O)C[C@@H](C(=O)CF)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)OCC1=CC=CC=C1 MIFGOLAMNLSLGH-QOKNQOGYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000036523 atherogenesis Effects 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- MDDIUTVUBYEEEM-UHFFFAOYSA-N azane;pyrrolidine-1-carbodithioic acid Chemical compound N.SC(=S)N1CCCC1 MDDIUTVUBYEEEM-UHFFFAOYSA-N 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229950010527 belnacasan Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000010378 bimolecular fluorescence complementation Methods 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
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 125000003636 chemical group Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 210000003040 circulating cell Anatomy 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000013211 curve analysis Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 230000035614 depigmentation Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical class C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000003173 enzyme complementation Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 238000007421 fluorometric assay Methods 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 108091008147 housekeeping proteins Proteins 0.000 description 1
- 102000052620 human IL10 Human genes 0.000 description 1
- 102000051001 human MEFV Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000008088 immune pathway Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000010507 innate immune sensing pathway Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940126181 ion channel inhibitor Drugs 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229960001614 levamisole Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000010859 live-cell imaging Methods 0.000 description 1
- 230000005817 liver abnormality Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000011880 melting curve analysis Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- PHLCQASLWHYEMX-DEKIMQJDSA-N methyl (4s)-5-[[(2s,3r)-1-[[(3s)-5-fluoro-1-methoxy-1,4-dioxopentan-3-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-[[(2s,3s)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-oxopentanoate Chemical compound COC(=O)C[C@@H](C(=O)CF)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(=O)OC)NC(=O)[C@H]([C@@H](C)CC)NC(=O)OCC1=CC=CC=C1 PHLCQASLWHYEMX-DEKIMQJDSA-N 0.000 description 1
- 108091059501 miR-320a stem-loop Proteins 0.000 description 1
- 108091088570 miR-320a-1 stem-loop Proteins 0.000 description 1
- 108091070041 miR-320a-2 stem-loop Proteins 0.000 description 1
- 108091065447 miR-320a-3 stem-loop Proteins 0.000 description 1
- 108091054114 miR-320a-4 stem-loop Proteins 0.000 description 1
- 108091080700 miR-484 stem-loop Proteins 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000009343 monoculture Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical compound N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 210000005157 neural retina Anatomy 0.000 description 1
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- KTEXNACQROZXEV-PVLRGYAZSA-N parthenolide Chemical compound C1CC(/C)=C/CC[C@@]2(C)O[C@@H]2[C@H]2OC(=O)C(=C)[C@@H]21 KTEXNACQROZXEV-PVLRGYAZSA-N 0.000 description 1
- 229940069510 parthenolide Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 210000000680 phagosome Anatomy 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 229950000362 pralnacasan Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 208000019539 pyogenic bacterial infections due to MyD88 deficiency Diseases 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000004258 retinal degeneration Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
- A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
- G01N33/5023—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects on expression patterns
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
- G01N33/5041—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects involving analysis of members of signalling pathways
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
- G01N33/6869—Interleukin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- General Physics & Mathematics (AREA)
- Toxicology (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Engineering & Computer Science (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161508867P | 2011-07-18 | 2011-07-18 | |
| US61/508,867 | 2011-07-18 | ||
| US201161543038P | 2011-10-04 | 2011-10-04 | |
| US61/543,038 | 2011-10-04 | ||
| CA2842034A CA2842034C (en) | 2011-07-18 | 2012-07-16 | Protection of cells from alu-rna-induced degeneration and inhibitors for protecting cells |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2842034A Division CA2842034C (en) | 2011-07-18 | 2012-07-16 | Protection of cells from alu-rna-induced degeneration and inhibitors for protecting cells |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3205596A1 true CA3205596A1 (en) | 2013-01-24 |
Family
ID=47558691
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3205596A Pending CA3205596A1 (en) | 2011-07-18 | 2012-07-16 | Protection of cells from alu-rna-induced degeneration and inhibitors for protecting cells |
| CA2842034A Active CA2842034C (en) | 2011-07-18 | 2012-07-16 | Protection of cells from alu-rna-induced degeneration and inhibitors for protecting cells |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2842034A Active CA2842034C (en) | 2011-07-18 | 2012-07-16 | Protection of cells from alu-rna-induced degeneration and inhibitors for protecting cells |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9453226B2 (cg-RX-API-DMAC7.html) |
| EP (2) | EP2734240B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6313203B2 (cg-RX-API-DMAC7.html) |
| CN (1) | CN103889461B (cg-RX-API-DMAC7.html) |
| AU (1) | AU2012284223B2 (cg-RX-API-DMAC7.html) |
| CA (2) | CA3205596A1 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2907620T3 (cg-RX-API-DMAC7.html) |
| PT (1) | PT3366302T (cg-RX-API-DMAC7.html) |
| WO (1) | WO2013012806A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010138555A2 (en) | 2009-05-26 | 2010-12-02 | University Of Florida Research Foundation, Inc. | Small peptide expression system in mammalian cells |
| ES2732929T3 (es) | 2010-10-22 | 2019-11-26 | Olix Pharmaceuticals Inc | Moléculas de ácido nucleico que inducen interferencia de ARN y usos de las mismas |
| US9707235B1 (en) * | 2012-01-13 | 2017-07-18 | University Of Kentucky Research Foundation | Protection of cells from degeneration and treatment of geographic atrophy |
| WO2013169382A1 (en) * | 2012-05-07 | 2013-11-14 | DePuy Synthes Products, LLC | Methods and devices for treating intervertebral disc disease |
| EP3514236A1 (en) | 2012-05-22 | 2019-07-24 | Olix Pharmaceuticals, Inc. | Rna-interference-inducing nucleic acid molecule able to penetrate into cells, and use therefor |
| WO2014039696A2 (en) | 2012-09-05 | 2014-03-13 | Cold Spring Harbor Laboratory | Transposable elements, tdp-43, and neurodegenerative disorders |
| EP2968613B1 (en) | 2013-03-11 | 2019-09-11 | University of Florida Research Foundation, Inc. | Delivery of card protein as therapy for occular inflammation |
| US9326983B2 (en) | 2013-08-01 | 2016-05-03 | University Of Kentucky Research Foundation | Compositions and methods for treating retinal degradation |
| WO2015095609A1 (en) * | 2013-12-19 | 2015-06-25 | The J. David Gladstone Institute | Inhibition of interferon-gamma-inducible protein 16 (ifi16) |
| US11053291B2 (en) | 2014-02-19 | 2021-07-06 | University Of Florida Research Foundation, Incorporated | Delivery of Nrf2 as therapy for protection against reactive oxygen species |
| WO2015138628A1 (en) * | 2014-03-11 | 2015-09-17 | University Of Florida Research Foundation, Inc. | Use of aav-expressed m013 protein as an anti-inflammatory therapeutic |
| WO2016022914A1 (en) * | 2014-08-08 | 2016-02-11 | Moderna Therapeutics, Inc. | Compositions and methods for the treatment of ophthalmic diseases and conditions |
| ES2879678T3 (es) | 2015-02-26 | 2021-11-22 | Univ Kentucky Res Found | Composiciones y procedimientos para el tratamiento de la degradación retiniana |
| US11219623B2 (en) | 2015-02-26 | 2022-01-11 | University Of Kentucky Research Foundation | Inflammasome inhibition for the treatment of Parkinson's disease, Alzheimer's disease and multiple sclerosis |
| CA2997516C (en) | 2015-09-03 | 2024-02-06 | B.G. Negev Technologies And Applications Ltd., At Ben-Gurion University | Analogues of vdac1-derived peptides |
| EP3373939A4 (en) * | 2015-11-10 | 2019-06-26 | B.G. Negev Technologies and Applications Ltd., at Ben-Gurion University | MEDIUM AND METHOD FOR REDUCING TUMORIGENITY OF CANCER STEM CELLS |
| EP3377630A4 (en) | 2015-11-16 | 2020-01-01 | Olix Pharmaceuticals, Inc. | Treatment of age-related macular degeneration using rna complexes that target myd88 or tlr3 |
| JP6944942B2 (ja) | 2016-02-02 | 2021-10-06 | オリックス ファーマシューティカルズ，インコーポレーテッド | ＩＬ４Ｒα、ＴＲＰＡ１、またはＦ２ＲＬ１を標的とするＲＮＡ複合体を用いたアトピー性皮膚炎および喘息の治療 |
| WO2017212477A1 (en) * | 2016-06-07 | 2017-12-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Backbone cyclized inhibitory peptides of myeloid differentiation factor 88 (myd88) |
| US11130951B2 (en) * | 2016-06-09 | 2021-09-28 | The General Hospital Corporation | Modulating the cellular stress response |
| KR101916652B1 (ko) | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
| US20190185820A1 (en) * | 2016-08-26 | 2019-06-20 | The Regents Of The University Of California | Compositions and Methods for Inhibiting Stem Cell Aging |
| ES2950100T3 (es) | 2016-12-23 | 2023-10-05 | Casp Aid Inc | Inhibición de la caspasa-1 y usos de esta para la prevención y el tratamiento de afecciones neurológicas |
| JP7424728B2 (ja) | 2017-02-10 | 2024-01-30 | オリック パルマセゥティカルズ インコーポレイテッド | Ｒｎａ干渉のための長鎖の二本鎖ｒｎａ |
| GB2561540A (en) | 2017-03-13 | 2018-10-24 | Nodthera Ltd | Chemical compounds |
| US11613756B2 (en) * | 2017-04-03 | 2023-03-28 | Duke University | Compositions and methods for differential induction of cell death and interferon expression |
| US20200345756A1 (en) * | 2017-10-10 | 2020-11-05 | University Of Virginia Patent Foundation | Compositions and methods for treating age-related macular degeneration and geographic atrophy |
| CN112512515B (zh) * | 2018-06-27 | 2025-10-10 | 儿童医学中心公司 | 用于抑制炎症的化合物 |
| KR102138256B1 (ko) * | 2018-09-13 | 2020-08-13 | 한국과학기술연구원 | 케스페이즈-1 활성 측정용 프로브, 이를 포함하는 염증성 질환 진단용 조성물 |
| US20210348164A1 (en) * | 2018-10-09 | 2021-11-11 | University Of Virginia Patent Foundation | Endogenous cytoplasmic alu complementary dna in age-related macular degeneration |
| CN110305957B (zh) * | 2019-08-22 | 2022-07-29 | 中国水产科学研究院淡水渔业研究中心 | 一种鉴定黄颡鱼脂肪肝程度的试剂盒及其鉴定方法 |
| CN114599373A (zh) * | 2019-08-23 | 2022-06-07 | 弗吉尼亚大学专利基金会 | 靶向炎性疾病的ddx17和nlrc4 |
| JP7459298B2 (ja) * | 2020-01-06 | 2024-04-01 | シーサン・セラピューティクス | 細胞透過性核酸複合体を有効成分として含有する黄斑変性の予防又は治療用組成物 |
| WO2021163327A1 (en) * | 2020-02-11 | 2021-08-19 | University Of Virginia Patent Foundation | Compositions and methods for treating and/or preventing ocular disorders |
| CN111358950A (zh) * | 2020-03-20 | 2020-07-03 | 厦门大学 | Caspase-1及ASC/Caspase-8作为靶点的应用 |
| US20240011030A1 (en) * | 2020-08-10 | 2024-01-11 | Novartis Ag | Treatments for retinal degenerative diseases |
| TW202233237A (zh) | 2020-11-18 | 2022-09-01 | 瑞士商諾華公司 | 用於在治療ｎｌｒｃ４－ｇｏｆ炎性體病變中使用的雙特異性抗體 |
| CN114099683B (zh) * | 2021-12-28 | 2022-12-16 | 首都医科大学附属北京同仁医院 | Nox2特异性抑制剂在制备视网膜变性药物中的应用 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2276216A1 (en) * | 1998-06-24 | 1999-12-24 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | An artificial peptide capable of neutralizing the biological activity of interleukin-18 |
| WO2000047218A1 (en) * | 1999-02-11 | 2000-08-17 | The Trustees Of The University Of Pennsylvania | Regulation of photoreceptor degeneration |
| GB9930616D0 (en) * | 1999-12-24 | 2000-02-16 | Mathilda & Terence Kennedy Ins | Activation and inhibition of the immune system |
| US20030186903A1 (en) * | 2001-11-23 | 2003-10-02 | Isis Pharmaceuticals Inc. | Antisense modulation of MyD88 expression |
| EP1474444A1 (en) * | 2002-01-10 | 2004-11-10 | Vlaams Interuniversitair Instituut voor Biotechnologie vzw. | A novel splice variant of myd88 and uses thereof |
| WO2006006948A2 (en) * | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
| US8090542B2 (en) * | 2002-11-14 | 2012-01-03 | Dharmacon Inc. | Functional and hyperfunctional siRNA |
| US9549895B2 (en) * | 2004-04-23 | 2017-01-24 | Massachusetts Eye And Ear Infirmary | Methods and compositions for preserving the viability of photoreceptor cells |
| BRPI0519148A2 (pt) | 2004-12-20 | 2008-12-30 | Sigma Tau Ind Farmaceuti | inibidores de homodimerizaÇço de myd88 |
| US7879992B2 (en) * | 2005-01-31 | 2011-02-01 | Isis Pharmaceuticals, Inc. | Modification of MyD88 splicing using modified oligonucleotides |
| EP1746167A1 (en) * | 2005-07-20 | 2007-01-24 | Apoxis SA | Method for the identification of compounds susceptible to inhibit inflammation |
| WO2007077042A1 (en) * | 2006-01-06 | 2007-07-12 | Topotarget Switzerland Sa | New method for the treatment of gout or pseudogout |
| WO2008070579A2 (en) | 2006-12-01 | 2008-06-12 | Loma Linda University Medical Center | Inhibition of brain enzymes involved in cerebral amyloid angiopathy and macular degeneration |
| AU2008260572A1 (en) * | 2007-05-29 | 2008-12-11 | Yale University | IL- 18 and protein kinase R inhibition for the treatment of COPD |
| US20090227487A1 (en) * | 2008-03-05 | 2009-09-10 | Jeremy Pearl | Methods for the control of macrophage-associated inflammation |
| JP2011530293A (ja) * | 2008-08-08 | 2011-12-22 | イデラ ファーマシューティカルズ インコーポレイテッド | アンチセンスオリゴヌクレオチドによる骨髄細胞分化初期応答遺伝子８８（ｍｙｄ８８）発現の調節 |
| US20130137642A1 (en) * | 2010-04-23 | 2013-05-30 | Demetrios Vavvas | Methods and compositions for preserving photoreceptor and retinal pigment epithelial cells |
| WO2011153234A2 (en) | 2010-06-01 | 2011-12-08 | University Of Kentucky Research Foundation | Methods of inhibiting alu rna and therapeutic uses thereof |
| US20120177632A1 (en) * | 2011-01-10 | 2012-07-12 | Shinohara Mari L | Methods of optimizing disease treatment |
-
2012
- 2012-07-16 CA CA3205596A patent/CA3205596A1/en active Pending
- 2012-07-16 CA CA2842034A patent/CA2842034C/en active Active
- 2012-07-16 ES ES18156266T patent/ES2907620T3/es active Active
- 2012-07-16 EP EP12814249.4A patent/EP2734240B1/en active Active
- 2012-07-16 JP JP2014521695A patent/JP6313203B2/ja active Active
- 2012-07-16 CN CN201280045438.0A patent/CN103889461B/zh active Active
- 2012-07-16 WO PCT/US2012/046928 patent/WO2013012806A2/en not_active Ceased
- 2012-07-16 PT PT181562661T patent/PT3366302T/pt unknown
- 2012-07-16 EP EP18156266.1A patent/EP3366302B1/en active Active
- 2012-07-16 AU AU2012284223A patent/AU2012284223B2/en active Active
-
2014
- 2014-01-17 US US14/158,357 patent/US9453226B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20140178309A1 (en) | 2014-06-26 |
| US9453226B2 (en) | 2016-09-27 |
| CA2842034C (en) | 2023-09-05 |
| CA2842034A1 (en) | 2013-01-24 |
| WO2013012806A3 (en) | 2013-05-30 |
| EP2734240A4 (en) | 2015-06-10 |
| PT3366302T (pt) | 2022-03-07 |
| ES2907620T3 (es) | 2022-04-25 |
| CN103889461A (zh) | 2014-06-25 |
| EP2734240B1 (en) | 2018-03-21 |
| EP3366302A1 (en) | 2018-08-29 |
| JP6313203B2 (ja) | 2018-04-18 |
| JP2014528700A (ja) | 2014-10-30 |
| AU2012284223A1 (en) | 2014-02-06 |
| EP2734240A2 (en) | 2014-05-28 |
| CN103889461B (zh) | 2016-11-09 |
| EP3366302B1 (en) | 2021-12-08 |
| AU2012284223B2 (en) | 2017-06-22 |
| WO2013012806A2 (en) | 2013-01-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2842034C (en) | Protection of cells from alu-rna-induced degeneration and inhibitors for protecting cells | |
| US11730743B2 (en) | Protection of cells from degeneration and treatment of geographic atrophy | |
| Tarallo et al. | DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88 | |
| Kerur et al. | TLR-independent and P2X7-dependent signaling mediate Alu RNA-induced NLRP3 inflammasome activation in geographic atrophy | |
| Pfalzgraff et al. | LPS-neutralizing peptides reduce outer membrane vesicle-induced inflammatory responses | |
| EP2340040B1 (en) | Modulation of axon degeneration | |
| US12274701B2 (en) | Compositions and methods for treating retinal degradation | |
| Yang et al. | White spot syndrome virus infection activates Caspase 1-mediated cell death in crustacean | |
| Ding et al. | Alamandine, a new member of the renin-angiotensin system (RAS), attenuates collagen-induced arthritis in mice via inhibiting cytokine secretion in synovial fibroblasts | |
| Latreille | Identification of a novel anti-inflammatory compound that acts via the Nrf2 pathway | |
| Chan | Macrophage Response to Interleukin-1 Stimulation and the Nature of Cell Surface Interleukin-1 Alpha | |
| Kasumba | A plant-derived nucleic acid protects mice from respiratory viruses in an IFN-I-dependent and independent manner | |
| Rathkey | Gasdermin D as the Effector of Pyroptotic Cell Death | |
| Marrero | Investigating Cell Type-Specific Responses to Legionella pneumophila Infection | |
| Heir | Glial tumour necrosis factor in synaptic scaling and the regulation of immune molecules by neuronal activity | |
| Suen | Circulating MicroRNAs Trigger Innate Immune Activation in Polytraumatic Injury | |
| Lê-Bury et al. | The unique lipopolysaccharide composition of Salmonella Typhimurium ST313 dampens pyroptosis and inflammasome activation and suppresses host cell death | |
| Apel | Recognition of Neutrophil Extracellular Traps by the Cytosolic DNA Sensor cGAS | |
| Rodemer | Interactions between the axon tip and its environment in regulating neuronal survival and axon regeneration: roles of the CSPG receptor, PTPσ, and delayed axolemmal resealing. | |
| Lei | Biochemical and functional characterization of the mitochondrial immune Signaling protein complex | |
| Deplano | Role of P2X7-Mediated Inflammasome Activation in Glomerulonephritis | |
| Kerminen | Innate Immune Recognition of RNA-Virus Infection in Human Macrophages |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20230704 |
|
| EEER | Examination request |
Effective date: 20230704 |
|
| EEER | Examination request |
Effective date: 20230704 |