CA2630932A1 - Multitargeting interfering rnas and methods of their use and design - Google Patents
Multitargeting interfering rnas and methods of their use and design Download PDFInfo
- Publication number
- CA2630932A1 CA2630932A1 CA002630932A CA2630932A CA2630932A1 CA 2630932 A1 CA2630932 A1 CA 2630932A1 CA 002630932 A CA002630932 A CA 002630932A CA 2630932 A CA2630932 A CA 2630932A CA 2630932 A1 CA2630932 A1 CA 2630932A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- rna molecule
- rna
- target
- interfering 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.)
- Abandoned
Links
- 230000002452 interceptive effect Effects 0.000 title claims abstract description 186
- 108091032973 (ribonucleotides)n+m Proteins 0.000 title claims description 720
- 238000000034 method Methods 0.000 title claims description 85
- 102000040650 (ribonucleotides)n+m Human genes 0.000 title description 87
- 238000013461 design Methods 0.000 title description 29
- 230000014509 gene expression Effects 0.000 claims abstract description 145
- 230000027455 binding Effects 0.000 claims abstract description 101
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 65
- 230000002068 genetic effect Effects 0.000 claims abstract description 45
- 230000000694 effects Effects 0.000 claims description 148
- 239000002773 nucleotide Substances 0.000 claims description 58
- 125000003729 nucleotide group Chemical group 0.000 claims description 56
- 230000000295 complement effect Effects 0.000 claims description 51
- 241000700605 Viruses Species 0.000 claims description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 49
- 102000004169 proteins and genes Human genes 0.000 claims description 44
- 201000010099 disease Diseases 0.000 claims description 40
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 claims description 37
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 claims description 36
- 230000003993 interaction Effects 0.000 claims description 32
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 29
- 230000007423 decrease Effects 0.000 claims description 26
- 239000013598 vector Substances 0.000 claims description 23
- 108020004999 messenger RNA Proteins 0.000 claims description 21
- 238000012360 testing method Methods 0.000 claims description 20
- 241001465754 Metazoa Species 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 18
- 230000009368 gene silencing by RNA Effects 0.000 claims description 16
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 14
- 239000004055 small Interfering RNA Substances 0.000 claims description 13
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 claims description 12
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 claims description 12
- 108090001007 Interleukin-8 Proteins 0.000 claims description 12
- 108091027967 Small hairpin RNA Proteins 0.000 claims description 11
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- 208000015181 infectious disease Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 9
- -1 BACE-1 Proteins 0.000 claims description 8
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims description 8
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 8
- 108091007767 MALAT1 Proteins 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 230000001413 cellular effect Effects 0.000 claims description 8
- 102000042567 non-coding RNA Human genes 0.000 claims description 8
- 108091027963 non-coding RNA Proteins 0.000 claims description 8
- 102100021943 C-C motif chemokine 2 Human genes 0.000 claims description 7
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims description 7
- 241000709661 Enterovirus Species 0.000 claims description 7
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 7
- 125000002652 ribonucleotide group Chemical group 0.000 claims description 7
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 claims description 6
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 6
- 102000040945 Transcription factor Human genes 0.000 claims description 6
- 108091023040 Transcription factor Proteins 0.000 claims description 6
- 125000002015 acyclic group Chemical group 0.000 claims description 6
- 239000013604 expression vector Substances 0.000 claims description 6
- 239000013603 viral vector Substances 0.000 claims description 6
- 108020005345 3' Untranslated Regions Proteins 0.000 claims description 5
- 208000035657 Abasia Diseases 0.000 claims description 5
- 108010078791 Carrier Proteins Proteins 0.000 claims description 5
- 108090001069 Chymopapain Proteins 0.000 claims description 5
- XXAXVMUWHZHZMJ-UHFFFAOYSA-N Chymopapain Chemical compound OC1=CC(S(O)(=O)=O)=CC(S(O)(=O)=O)=C1O XXAXVMUWHZHZMJ-UHFFFAOYSA-N 0.000 claims description 5
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 claims description 5
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 claims description 5
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 claims description 5
- 239000000427 antigen Substances 0.000 claims description 5
- 108091007433 antigens Proteins 0.000 claims description 5
- 102000036639 antigens Human genes 0.000 claims description 5
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 5
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 5
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 102000010831 Cytoskeletal Proteins Human genes 0.000 claims description 4
- 108010037414 Cytoskeletal Proteins Proteins 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 claims description 4
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 claims description 4
- 102100035194 Placenta growth factor Human genes 0.000 claims description 4
- 108091028664 Ribonucleotide Proteins 0.000 claims description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 4
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 claims description 4
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 claims description 4
- 108020000999 Viral RNA Proteins 0.000 claims description 4
- 102000034356 gene-regulatory proteins Human genes 0.000 claims description 4
- 108091006104 gene-regulatory proteins Proteins 0.000 claims description 4
- 238000010348 incorporation Methods 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 230000002458 infectious effect Effects 0.000 claims description 4
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 4
- 239000002336 ribonucleotide Substances 0.000 claims description 4
- 241000712461 unidentified influenza virus Species 0.000 claims description 4
- 241001430294 unidentified retrovirus Species 0.000 claims description 4
- 241000710929 Alphavirus Species 0.000 claims description 3
- 108091035707 Consensus sequence Proteins 0.000 claims description 3
- 241000282326 Felis catus Species 0.000 claims description 3
- 102000004890 Interleukin-8 Human genes 0.000 claims description 3
- 102000012412 Presenilin-1 Human genes 0.000 claims description 3
- 108010036933 Presenilin-1 Proteins 0.000 claims description 3
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 claims description 3
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 claims description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 3
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 claims description 3
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 claims description 3
- 230000028709 inflammatory response Effects 0.000 claims description 3
- 108020005065 3' Flanking Region Proteins 0.000 claims description 2
- 108020005029 5' Flanking Region Proteins 0.000 claims description 2
- 102100037151 Barrier-to-autointegration factor Human genes 0.000 claims description 2
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 2
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 2
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 2
- 241000702421 Dependoparvovirus Species 0.000 claims description 2
- 108090001126 Furin Proteins 0.000 claims description 2
- 101000740067 Homo sapiens Barrier-to-autointegration factor Proteins 0.000 claims description 2
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 2
- 241000713666 Lentivirus Species 0.000 claims description 2
- 241000701161 unidentified adenovirus Species 0.000 claims description 2
- 229940035893 uracil Drugs 0.000 claims description 2
- 241000711549 Hepacivirus C Species 0.000 claims 10
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 claims 5
- 241000315672 SARS coronavirus Species 0.000 claims 3
- 241000282693 Cercopithecidae Species 0.000 claims 2
- 102100036220 PC4 and SFRS1-interacting protein Human genes 0.000 claims 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims 2
- 102000003675 cytokine receptors Human genes 0.000 claims 2
- 108010057085 cytokine receptors Proteins 0.000 claims 2
- 239000005556 hormone Substances 0.000 claims 2
- 229940088597 hormone Drugs 0.000 claims 2
- 108091006024 signal transducing proteins Proteins 0.000 claims 2
- 102000034285 signal transducing proteins Human genes 0.000 claims 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims 1
- 102000004961 Furin Human genes 0.000 claims 1
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 claims 1
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 claims 1
- 108090000144 Human Proteins Proteins 0.000 claims 1
- 102000003839 Human Proteins Human genes 0.000 claims 1
- 108091036066 Three prime untranslated region Proteins 0.000 claims 1
- 229960005305 adenosine Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 108010093345 lens epithelium-derived growth factor Proteins 0.000 claims 1
- 230000003938 response to stress Effects 0.000 claims 1
- 238000013459 approach Methods 0.000 abstract description 11
- 210000004027 cell Anatomy 0.000 description 166
- 108020004459 Small interfering RNA Proteins 0.000 description 65
- 150000002500 ions Chemical class 0.000 description 36
- 230000003612 virological effect Effects 0.000 description 31
- 230000008685 targeting Effects 0.000 description 30
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 27
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 27
- 101100238304 Mus musculus Morc1 gene Proteins 0.000 description 25
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 24
- 239000002253 acid Substances 0.000 description 24
- 238000011068 loading method Methods 0.000 description 22
- 206010028980 Neoplasm Diseases 0.000 description 21
- 150000007523 nucleic acids Chemical class 0.000 description 21
- 238000003556 assay Methods 0.000 description 20
- 201000011510 cancer Diseases 0.000 description 20
- 102000039446 nucleic acids Human genes 0.000 description 18
- 108020004707 nucleic acids Proteins 0.000 description 18
- 230000001629 suppression Effects 0.000 description 18
- 101000574648 Homo sapiens Retinoid-inducible serine carboxypeptidase Proteins 0.000 description 17
- 102100025483 Retinoid-inducible serine carboxypeptidase Human genes 0.000 description 17
- 108020004414 DNA Proteins 0.000 description 16
- 101710113436 GTPase KRas Proteins 0.000 description 16
- 230000004048 modification Effects 0.000 description 15
- 238000012986 modification Methods 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 14
- 238000001890 transfection Methods 0.000 description 14
- 230000008569 process Effects 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 12
- 238000009396 hybridization Methods 0.000 description 12
- 241000196324 Embryophyta Species 0.000 description 11
- 239000002679 microRNA Substances 0.000 description 11
- 108091030071 RNAI Proteins 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 230000015556 catabolic process Effects 0.000 description 9
- 238000006731 degradation reaction Methods 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 108090000672 Annexin A5 Proteins 0.000 description 7
- 102000004121 Annexin A5 Human genes 0.000 description 7
- 101150093222 CTTN gene Proteins 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 7
- 108700011259 MicroRNAs Proteins 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 210000003414 extremity Anatomy 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- 230000014616 translation Effects 0.000 description 7
- 241000700159 Rattus Species 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000030279 gene silencing Effects 0.000 description 6
- 238000000126 in silico method Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- JEPVUMTVFPQKQE-AAKCMJRZSA-N 2-[(1s,2s,3r,4s)-1,2,3,4,5-pentahydroxypentyl]-1,3-thiazolidine-4-carboxylic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C1NC(C(O)=O)CS1 JEPVUMTVFPQKQE-AAKCMJRZSA-N 0.000 description 5
- 108050002340 Annexin A13 Proteins 0.000 description 5
- 102100039951 Annexin A13 Human genes 0.000 description 5
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 5
- 229930010555 Inosine Natural products 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 229960003786 inosine Drugs 0.000 description 5
- 230000009249 intrinsic sympathomimetic activity Effects 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 108091093088 Amplicon Proteins 0.000 description 4
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 108091070501 miRNA Proteins 0.000 description 4
- 230000009437 off-target effect Effects 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 210000001525 retina Anatomy 0.000 description 4
- 230000002207 retinal effect Effects 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- 108010076667 Caspases Proteins 0.000 description 3
- 102000011727 Caspases Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 208000005176 Hepatitis C Diseases 0.000 description 3
- 101000830596 Homo sapiens Tumor necrosis factor ligand superfamily member 15 Proteins 0.000 description 3
- 241000283986 Lepus Species 0.000 description 3
- 230000004570 RNA-binding Effects 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 108020003224 Small Nucleolar RNA Proteins 0.000 description 3
- 102000042773 Small Nucleolar RNA Human genes 0.000 description 3
- 102100024587 Tumor necrosis factor ligand superfamily member 15 Human genes 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 230000002491 angiogenic effect Effects 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000010432 diamond Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 241001493065 dsRNA viruses Species 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 235000001968 nicotinic acid Nutrition 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012827 research and development Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- 101150073075 Chrm1 gene Proteins 0.000 description 2
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 2
- 102100036044 Conserved oligomeric Golgi complex subunit 4 Human genes 0.000 description 2
- 101000936738 Coturnix japonica Astacin-like metalloendopeptidase Proteins 0.000 description 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 2
- 102100022266 DnaJ homolog subfamily C member 22 Human genes 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 101000876012 Homo sapiens Conserved oligomeric Golgi complex subunit 4 Proteins 0.000 description 2
- 101000946124 Homo sapiens Lipocalin-1 Proteins 0.000 description 2
- 101001104102 Homo sapiens X-linked retinitis pigmentosa GTPase regulator Proteins 0.000 description 2
- 108091065449 Homo sapiens miR-299 stem-loop Proteins 0.000 description 2
- 102100034724 Lipocalin-1 Human genes 0.000 description 2
- 101000794562 Naegleria gruberi Calmodulin, flagellar Proteins 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 101000941356 Nostoc ellipsosporum Cyanovirin-N Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 208000036448 RPGR-related retinopathy Diseases 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 102000039471 Small Nuclear RNA Human genes 0.000 description 2
- 241001599630 Stelis <bee> Species 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 108700012920 TNF Proteins 0.000 description 2
- 240000006909 Tilia x europaea Species 0.000 description 2
- 235000011941 Tilia x europaea Nutrition 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 108020004566 Transfer RNA Proteins 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 201000000467 X-linked cone-rod dystrophy 1 Diseases 0.000 description 2
- 241000607479 Yersinia pestis Species 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000006364 cellular survival Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000012297 crystallization seed Substances 0.000 description 2
- 238000012938 design process Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000004571 lime Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 108091028606 miR-1 stem-loop Proteins 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000001023 pro-angiogenic effect Effects 0.000 description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 description 2
- 210000001747 pupil Anatomy 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 102220018940 rs80358547 Human genes 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 101150115956 slc25a26 gene Proteins 0.000 description 2
- 108091029842 small nuclear ribonucleic acid Proteins 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- HCGYMSSYSAKGPK-UHFFFAOYSA-N 2-nitro-1h-indole Chemical compound C1=CC=C2NC([N+](=O)[O-])=CC2=C1 HCGYMSSYSAKGPK-UHFFFAOYSA-N 0.000 description 1
- LOJNBPNACKZWAI-UHFFFAOYSA-N 3-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C=1C=CNC=1 LOJNBPNACKZWAI-UHFFFAOYSA-N 0.000 description 1
- YPSXFMHXRZAGTG-UHFFFAOYSA-N 4-methoxy-2-[2-(5-methoxy-2-nitrosophenyl)ethyl]-1-nitrosobenzene Chemical compound COC1=CC=C(N=O)C(CCC=2C(=CC=C(OC)C=2)N=O)=C1 YPSXFMHXRZAGTG-UHFFFAOYSA-N 0.000 description 1
- 241000023308 Acca Species 0.000 description 1
- 241001377084 Actites Species 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 102100039375 Ankyrin repeat domain-containing protein 2 Human genes 0.000 description 1
- 101100480489 Arabidopsis thaliana TAAC gene Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101710125089 Bindin Proteins 0.000 description 1
- 241001674044 Blattodea Species 0.000 description 1
- 101100537937 Caenorhabditis elegans arc-1 gene Proteins 0.000 description 1
- 101100504320 Caenorhabditis elegans mcp-1 gene Proteins 0.000 description 1
- 101100237797 Caenorhabditis elegans mlk-1 gene Proteins 0.000 description 1
- 101100476210 Caenorhabditis elegans rnt-1 gene Proteins 0.000 description 1
- 101100421200 Caenorhabditis elegans sep-1 gene Proteins 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000206575 Chondrus crispus Species 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 241000272470 Circus Species 0.000 description 1
- 241000543381 Cliftonia monophylla Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000218631 Coniferophyta Species 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 101150005261 Cul7 gene Proteins 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 101100477524 Danio rerio inppl1b gene Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 101100130497 Drosophila melanogaster Mical gene Proteins 0.000 description 1
- 101100456896 Drosophila melanogaster metl gene Proteins 0.000 description 1
- 101100346656 Drosophila melanogaster strat gene Proteins 0.000 description 1
- 102100021238 Dynamin-2 Human genes 0.000 description 1
- 102100038509 E3 ubiquitin-protein ligase ARIH1 Human genes 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101100233116 Escherichia coli insC gene Proteins 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 102100037091 Exonuclease V Human genes 0.000 description 1
- 101150081880 FGF1 gene Proteins 0.000 description 1
- 229920006358 Fluon Polymers 0.000 description 1
- 102100035233 Furin Human genes 0.000 description 1
- 102100035189 GPI ethanolamine phosphate transferase 1 Human genes 0.000 description 1
- 241000276484 Gadus ogac Species 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000961307 Homo sapiens Ankyrin repeat domain-containing protein 2 Proteins 0.000 description 1
- 101000817607 Homo sapiens Dynamin-2 Proteins 0.000 description 1
- 101000808922 Homo sapiens E3 ubiquitin-protein ligase ARIH1 Proteins 0.000 description 1
- 101000881977 Homo sapiens Exonuclease V Proteins 0.000 description 1
- 101001093751 Homo sapiens GPI ethanolamine phosphate transferase 1 Proteins 0.000 description 1
- 101000869690 Homo sapiens Protein S100-A8 Proteins 0.000 description 1
- 101100077149 Human herpesvirus 8 type P (isolate GK18) K5 gene Proteins 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 101150007193 IFNB1 gene Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000764773 Inna Species 0.000 description 1
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
- 241000726306 Irus Species 0.000 description 1
- 108091032995 L1Base Proteins 0.000 description 1
- 101100464256 Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e) plcA gene Proteins 0.000 description 1
- 101150004219 MCR1 gene Proteins 0.000 description 1
- 108091007775 MIR1-1 Proteins 0.000 description 1
- 108091046841 MiR-150 Proteins 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100162168 Mus musculus Adam1a gene Proteins 0.000 description 1
- 101100384355 Mus musculus Ctnnbip1 gene Proteins 0.000 description 1
- 101100345589 Mus musculus Mical1 gene Proteins 0.000 description 1
- 101100084155 Mus musculus Prpf40b gene Proteins 0.000 description 1
- 101100425017 Mus musculus Qtrt1 gene Proteins 0.000 description 1
- 101100141312 Mus musculus Ripk1 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241001508687 Mustela erminea Species 0.000 description 1
- PKFBJSDMCRJYDC-GEZSXCAASA-N N-acetyl-s-geranylgeranyl-l-cysteine Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CSC[C@@H](C(O)=O)NC(C)=O PKFBJSDMCRJYDC-GEZSXCAASA-N 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 101100338491 Oryza sativa subsp. japonica HCT1 gene Proteins 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 241001257017 Platytes Species 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102100032442 Protein S100-A8 Human genes 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108020005093 RNA Precursors Proteins 0.000 description 1
- 238000010357 RNA editing Methods 0.000 description 1
- 230000026279 RNA modification Effects 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 101100322557 Rattus norvegicus Adam1 gene Proteins 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 108010044012 STAT1 Transcription Factor Proteins 0.000 description 1
- 102000006381 STAT1 Transcription Factor Human genes 0.000 description 1
- 101100495309 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CDH1 gene Proteins 0.000 description 1
- 206010039580 Scar Diseases 0.000 description 1
- 235000014328 Schoenoplectus acutus var occidentalis Nutrition 0.000 description 1
- 244000136421 Scirpus acutus Species 0.000 description 1
- 235000014326 Scirpus californicus Nutrition 0.000 description 1
- 235000017913 Scirpus lacustris Nutrition 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 101150092978 Slc25a4 gene Proteins 0.000 description 1
- 108091060271 Small temporal RNA Proteins 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 101100287028 Solanum lycopersicum ARPI gene Proteins 0.000 description 1
- 101000882406 Staphylococcus aureus Enterotoxin type C-1 Proteins 0.000 description 1
- UZHDGDDPOPDJGM-UHFFFAOYSA-N Stigmatellin A Natural products COC1=CC(OC)=C2C(=O)C(C)=C(CCC(C)C(OC)C(C)C(C=CC=CC(C)=CC)OC)OC2=C1O UZHDGDDPOPDJGM-UHFFFAOYSA-N 0.000 description 1
- 101100260761 Streptomyces fradiae tlrC gene Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 1
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 description 1
- 102000008230 Toll-like receptor 3 Human genes 0.000 description 1
- 108010060885 Toll-like receptor 3 Proteins 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- 241000508780 Tomato infectious chlorosis virus Species 0.000 description 1
- 241000625014 Vir Species 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004155 blood-retinal barrier Anatomy 0.000 description 1
- 230000004378 blood-retinal barrier Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 108010031234 carbon monoxide dehydrogenase Proteins 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004098 cellular respiration Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 101150084890 cstA gene Proteins 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 238000011393 cytotoxic chemotherapy Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- NJDNXYGOVLYJHP-UHFFFAOYSA-L disodium;2-(3-oxido-6-oxoxanthen-9-yl)benzoate Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=CC(=O)C=C2OC2=CC([O-])=CC=C21 NJDNXYGOVLYJHP-UHFFFAOYSA-L 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 101150089204 easF gene Proteins 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 241001233957 eudicotyledons Species 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N ferric oxide Chemical compound O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 101150111011 ficd gene Proteins 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- PLHJDBGFXBMTGZ-WEVVVXLNSA-N furazolidone Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)OCC1 PLHJDBGFXBMTGZ-WEVVVXLNSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- JCYWCSGERIELPG-UHFFFAOYSA-N imes Chemical class CC1=CC(C)=CC(C)=C1N1C=CN(C=2C(=CC(C)=CC=2C)C)[C]1 JCYWCSGERIELPG-UHFFFAOYSA-N 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 101150085091 lat-2 gene Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- DJGAAPFSPWAYTJ-UHFFFAOYSA-M metamizole sodium Chemical compound [Na+].O=C1C(N(CS([O-])(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 DJGAAPFSPWAYTJ-UHFFFAOYSA-M 0.000 description 1
- MHIGBKBJSQVXNH-IWVLMIASSA-N methacycline Chemical compound C=C([C@H]1[C@@H]2O)C3=CC=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O MHIGBKBJSQVXNH-IWVLMIASSA-N 0.000 description 1
- 108091044592 miR-1-1 stem-loop Proteins 0.000 description 1
- 108091049773 miR-14 stem-loop Proteins 0.000 description 1
- 108091057645 miR-15 stem-loop Proteins 0.000 description 1
- 108091078999 miR-56 stem-loop Proteins 0.000 description 1
- 108091078326 miR-71 stem-loop Proteins 0.000 description 1
- 108091045819 miR-82 stem-loop Proteins 0.000 description 1
- 108091092625 miR-87 stem-loop Proteins 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 108700004028 nef Genes Proteins 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000007959 normoxia Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- UOJMTSCORVQOHS-UHFFFAOYSA-N pachypodol Natural products COc1cc(ccc1O)C2=C(C)C(=O)c3c(O)cc(C)cc3O2 UOJMTSCORVQOHS-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000000649 photocoagulation Effects 0.000 description 1
- 101150086837 pic gene Proteins 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
- 230000004537 potential cytotoxicity Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 108010014186 ras Proteins Proteins 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004233 retinal vasculature Effects 0.000 description 1
- 102200025788 rs179363875 Human genes 0.000 description 1
- 208000014745 severe cutaneous adverse reaction Diseases 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 108091069025 single-strand RNA Proteins 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- GABUSZPTCJGKGB-UHFFFAOYSA-M sodium;4-(4-chloro-2-methylphenoxy)butanoate Chemical compound [Na+].CC1=CC(Cl)=CC=C1OCCCC([O-])=O GABUSZPTCJGKGB-UHFFFAOYSA-M 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 208000037918 transfusion-transmitted disease Diseases 0.000 description 1
- 230000009752 translational inhibition Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000001226 triphosphate Substances 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
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006711 vascular endothelial growth factor production Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7115—Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
-
- 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
- A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- 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
-
- 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
- C12N15/1131—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 viruses
- C12N15/1132—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 viruses against retroviridae, e.g. HIV
-
- 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
- C12N15/1135—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 oncogenes or tumor suppressor genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N15/1138—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 receptors or cell surface proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/50—Methods for regulating/modulating their activity
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73864005P | 2005-11-21 | 2005-11-21 | |
| US73844105P | 2005-11-21 | 2005-11-21 | |
| US60/738,640 | 2005-11-21 | ||
| US60/738,441 | 2005-11-21 | ||
| PCT/AU2006/001741 WO2007056826A1 (en) | 2005-11-21 | 2006-11-21 | Multitargeting interfering rnas and methods of their use and design |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2630932A1 true CA2630932A1 (en) | 2007-05-24 |
Family
ID=38048226
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002630932A Abandoned CA2630932A1 (en) | 2005-11-21 | 2006-11-21 | Multitargeting interfering rnas and methods of their use and design |
| CA002630952A Abandoned CA2630952A1 (en) | 2005-11-21 | 2006-11-21 | Multitargeting interfering rnas having two active strands and methods for their design and use |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002630952A Abandoned CA2630952A1 (en) | 2005-11-21 | 2006-11-21 | Multitargeting interfering rnas having two active strands and methods for their design and use |
Country Status (6)
| Country | Link |
|---|---|
| US (3) | US20070269815A1 (https=) |
| EP (2) | EP1951736A4 (https=) |
| JP (2) | JP2009516518A (https=) |
| AU (2) | AU2006315099C1 (https=) |
| CA (2) | CA2630932A1 (https=) |
| WO (2) | WO2007056826A1 (https=) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008053019A2 (en) * | 2006-11-02 | 2008-05-08 | Dsm Ip Assets B.V. | Method for reducing the expression of a gene in a filamentous fungal cell |
| US20120071539A1 (en) * | 2006-12-12 | 2012-03-22 | Emory University | Compounds and methods for modulating the silencing of a polynucleotide of interest |
| US8071752B2 (en) | 2007-01-29 | 2011-12-06 | City Of Hope | Multi-targeting short interfering RNAs |
| CA2679867A1 (en) * | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Nucleic acid compounds for inhibiting vegf family gene expression and uses thereof |
| WO2008109361A1 (en) * | 2007-03-02 | 2008-09-12 | Mdrna, Inc, | Nucleic acid compounds for inhibiting erbb family gene expression and uses thereof |
| US20080311040A1 (en) * | 2007-03-06 | 2008-12-18 | Flagship Ventures | METHODS AND COMPOSITIONS FOR IMPROVED THERAPEUTIC EFFECTS WITH siRNA |
| WO2008137862A2 (en) | 2007-05-03 | 2008-11-13 | Rosetta Inpharmatics Llc | Methods of using mir34 as a biomarker for tp53 functional status |
| EP2160191A4 (en) * | 2007-05-15 | 2011-06-29 | Johnson & Johnson Res Pty Ltd | SUPPRESSION OF VIRUSES INVOLVED IN A DISEASE OR RESPIRATORY INFECTION |
| WO2009035539A2 (en) | 2007-09-05 | 2009-03-19 | Nt Omics Inc. | Long interfering nucleic acid duplexes targeting multiple rna targets |
| US8097712B2 (en) | 2007-11-07 | 2012-01-17 | Beelogics Inc. | Compositions for conferring tolerance to viral disease in social insects, and the use thereof |
| JP5654352B2 (ja) | 2007-11-09 | 2015-01-14 | ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム | ｍｉＲ−１５ファミリーのマイクロＲＮＡによる心筋細胞生存及び心臓修復の調節 |
| GB2468477A (en) * | 2009-03-02 | 2010-09-15 | Mina Therapeutics Ltd | Double stranded RNA molecule comprising siRNA and miRNA precursors |
| CN107129998A (zh) | 2009-06-10 | 2017-09-05 | 淡马锡生命科学研究院有限公司 | 用于棉花中基因功能性分析的病毒诱导的基因沉默(vigs) |
| US8962584B2 (en) | 2009-10-14 | 2015-02-24 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | Compositions for controlling Varroa mites in bees |
| US20130023578A1 (en) * | 2009-12-31 | 2013-01-24 | Samyang Biopharmaceuticals Corporation | siRNA for inhibition of c-Met expression and anticancer composition containing the same |
| ES2641642T3 (es) | 2010-03-08 | 2017-11-10 | Monsanto Technology Llc | Moléculas de polinucleótido para regulación génica en plantas |
| AR083445A1 (es) | 2010-10-14 | 2013-02-27 | Univ Mie | siARN CONTRA LA FIBROSIS |
| US10806146B2 (en) | 2011-09-13 | 2020-10-20 | Monsanto Technology Llc | Methods and compositions for weed control |
| US10829828B2 (en) | 2011-09-13 | 2020-11-10 | Monsanto Technology Llc | Methods and compositions for weed control |
| US10760086B2 (en) | 2011-09-13 | 2020-09-01 | Monsanto Technology Llc | Methods and compositions for weed control |
| WO2013040057A1 (en) | 2011-09-13 | 2013-03-21 | Monsanto Technology Llc | Methods and compositions for weed control |
| HK1200484A1 (zh) | 2011-09-14 | 2015-08-07 | Translate Bio Ma, Inc. | 多聚寡核苷酸化合物 |
| ES2673960T3 (es) * | 2011-12-22 | 2018-06-26 | Ionis Pharmaceuticals, Inc. | Métodos para modular la expresión de un transcrito-1 de adenocarcinoma en pulmón asociado a metástasis (MALAT-1) |
| US9212363B2 (en) * | 2012-05-11 | 2015-12-15 | City Of Hope | RNAI molecules with non-watson crick pairing based on artificial mutation consensus sequences to counter escape mutations |
| JP2015523854A (ja) | 2012-05-16 | 2015-08-20 | ラナ セラピューティクス インコーポレイテッド | Ｓｍｎ遺伝子ファミリー発現を調節するための組成物及び方法 |
| CA2873766A1 (en) | 2012-05-16 | 2013-11-21 | Rana Therapeutics Inc. | Compositions and methods for modulating atp2a2 expression |
| US10837014B2 (en) | 2012-05-16 | 2020-11-17 | Translate Bio Ma, Inc. | Compositions and methods for modulating SMN gene family expression |
| CA2873769A1 (en) | 2012-05-16 | 2013-11-21 | Rana Therapeutics Inc. | Compositions and methods for modulating hemoglobin gene family expression |
| AU2013262709A1 (en) | 2012-05-16 | 2015-01-22 | Rana Therapeutics, Inc. | Compositions and methods for modulating MECP2 expression |
| BR112014028634A2 (pt) | 2012-05-16 | 2017-06-27 | Rana Therapeutics Inc | composições e métodos para modulação da expressão de utrn |
| MX360866B (es) | 2012-05-24 | 2018-11-09 | A B Seeds Ltd | Composiciones y métodos para silenciar la expresión genética. |
| US9163235B2 (en) | 2012-06-21 | 2015-10-20 | MiRagen Therapeutics, Inc. | Inhibitors of the miR-15 family of micro-RNAs |
| EP2895200B1 (en) | 2012-09-14 | 2019-11-06 | Translate Bio MA, Inc. | Multimeric oligonucleotide compounds |
| US10683505B2 (en) | 2013-01-01 | 2020-06-16 | Monsanto Technology Llc | Methods of introducing dsRNA to plant seeds for modulating gene expression |
| CN105143450A (zh) * | 2013-01-08 | 2015-12-09 | 贝尼泰克生物制药有限公司 | 年龄相关性黄斑变性治疗 |
| BR112015023051A2 (pt) | 2013-03-13 | 2017-11-14 | Monsanto Technology Llc | método para controle de ervas daninhas, composição herbicida, cassete de expressão microbiano e método de produção de polinucleotídeo |
| US10612019B2 (en) | 2013-03-13 | 2020-04-07 | Monsanto Technology Llc | Methods and compositions for weed control |
| US10568328B2 (en) | 2013-03-15 | 2020-02-25 | Monsanto Technology Llc | Methods and compositions for weed control |
| EP3030663B1 (en) | 2013-07-19 | 2019-09-04 | Monsanto Technology LLC | Compositions and methods for controlling leptinotarsa |
| US10174328B2 (en) | 2013-10-04 | 2019-01-08 | Translate Bio Ma, Inc. | Compositions and methods for treating amyotrophic lateral sclerosis |
| AU2014341879B2 (en) | 2013-11-04 | 2020-07-23 | Greenlight Biosciences, Inc. | Compositions and methods for controlling arthropod parasite and pest infestations |
| UA119253C2 (uk) | 2013-12-10 | 2019-05-27 | Біолоджикс, Інк. | Спосіб боротьби із вірусом у кліща varroa та у бджіл |
| WO2015108982A2 (en) | 2014-01-15 | 2015-07-23 | Monsanto Technology Llc | Methods and compositions for weed control using epsps polynucleotides |
| US9856475B2 (en) | 2014-03-25 | 2018-01-02 | Arcturus Therapeutics, Inc. | Formulations for treating amyloidosis |
| JP6771387B2 (ja) | 2014-03-25 | 2020-10-21 | アークトゥラス・セラピューティクス・インコーポレイテッドＡｒｃｔｕｒｕｓ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | 遺伝子サイレンシング用トランスサイレチン対立遺伝子選択的ｕｎａオリゴマー |
| WO2015148580A2 (en) * | 2014-03-25 | 2015-10-01 | Arcturus Therapeutics, Inc. | Una oligomers having reduced off-target effects in gene silencing |
| WO2015153339A2 (en) | 2014-04-01 | 2015-10-08 | Monsanto Technology Llc | Compositions and methods for controlling insect pests |
| CN106795515B (zh) * | 2014-06-23 | 2021-06-08 | 孟山都技术公司 | 用于经由rna干扰调控基因表达的组合物和方法 |
| US11807857B2 (en) | 2014-06-25 | 2023-11-07 | Monsanto Technology Llc | Methods and compositions for delivering nucleic acids to plant cells and regulating gene expression |
| CN106604993A (zh) | 2014-07-29 | 2017-04-26 | 孟山都技术公司 | 用于控制昆虫害虫的组合物和方法 |
| JP6726105B2 (ja) | 2014-12-15 | 2020-07-22 | 株式会社ボナック | ＴＧＦ−β１発現抑制のための一本鎖核酸分子 |
| CN108064288B (zh) | 2015-01-22 | 2021-11-26 | 孟山都技术公司 | 用于控制叶甲属的组合物和方法 |
| WO2016161299A1 (en) | 2015-04-01 | 2016-10-06 | Arcturus Therapeutics, Inc. | Therapeutic una oligomers and uses thereof |
| EP3302053B1 (en) | 2015-06-02 | 2021-03-17 | Monsanto Technology LLC | Compositions and methods for delivery of a polynucleotide into a plant |
| WO2016196782A1 (en) | 2015-06-03 | 2016-12-08 | Monsanto Technology Llc | Methods and compositions for introducing nucleic acids into plants |
| WO2017015671A1 (en) | 2015-07-23 | 2017-01-26 | Arcturus Therapeutics, Inc. | Compositions for treating amyloidosis |
| US10556019B2 (en) * | 2015-08-21 | 2020-02-11 | Universitätsklinikum Jena | Human microRNAs for treatment of malignant tumours |
| SG11201910115XA (en) * | 2017-05-01 | 2019-11-28 | Donald Danforth Plant Science Center | Rnai approach for crop pest protection |
| TW202540426A (zh) | 2019-02-27 | 2025-10-16 | 美商Ionis製藥公司 | Malat1表現之調節劑 |
| AU2022299474A1 (en) * | 2021-06-23 | 2023-12-21 | Versameb Ag | Compositions and methods for modulating expression of genes |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005019453A2 (en) * | 2001-05-18 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA) |
| US20050187174A1 (en) * | 2001-05-18 | 2005-08-25 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
| WO2003070912A2 (en) * | 2001-06-06 | 2003-08-28 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF EPIDERMAL GROWTH FACTOR RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US20050048529A1 (en) * | 2002-02-20 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
| US20050148530A1 (en) * | 2002-02-20 | 2005-07-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US20050209180A1 (en) * | 2001-05-18 | 2005-09-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA) |
| CN1738648A (zh) * | 2003-01-17 | 2006-02-22 | 佛罗里达大学研究基金会有限公司 | 小干扰rna基因治疗 |
| JP2008511678A (ja) * | 2004-09-02 | 2008-04-17 | イェール ユニバーシティ | マイクロｒｎａによるオンコジーンの調節 |
-
2006
- 2006-11-21 WO PCT/AU2006/001741 patent/WO2007056826A1/en not_active Ceased
- 2006-11-21 CA CA002630932A patent/CA2630932A1/en not_active Abandoned
- 2006-11-21 WO PCT/AU2006/001750 patent/WO2007056829A1/en not_active Ceased
- 2006-11-21 US US11/602,804 patent/US20070269815A1/en not_active Abandoned
- 2006-11-21 CA CA002630952A patent/CA2630952A1/en not_active Abandoned
- 2006-11-21 AU AU2006315099A patent/AU2006315099C1/en not_active Ceased
- 2006-11-21 EP EP06817512A patent/EP1951736A4/en not_active Withdrawn
- 2006-11-21 EP EP06817516A patent/EP1951263A4/en not_active Withdrawn
- 2006-11-21 JP JP2008541543A patent/JP2009516518A/ja not_active Ceased
- 2006-11-21 JP JP2008541541A patent/JP5078904B2/ja not_active Expired - Fee Related
- 2006-11-21 AU AU2006315102A patent/AU2006315102A1/en not_active Abandoned
-
2008
- 2008-05-21 US US12/124,590 patent/US20090239816A1/en not_active Abandoned
- 2008-05-21 US US12/124,629 patent/US8097715B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2630952A1 (en) | 2007-05-24 |
| EP1951736A4 (en) | 2009-12-16 |
| AU2006315099A1 (en) | 2007-05-24 |
| EP1951263A4 (en) | 2009-11-18 |
| EP1951736A1 (en) | 2008-08-06 |
| US20090192103A1 (en) | 2009-07-30 |
| AU2006315102A1 (en) | 2007-05-24 |
| US20070269815A1 (en) | 2007-11-22 |
| US8097715B2 (en) | 2012-01-17 |
| WO2007056826A1 (en) | 2007-05-24 |
| JP2009516518A (ja) | 2009-04-23 |
| JP2009516517A (ja) | 2009-04-23 |
| JP5078904B2 (ja) | 2012-11-21 |
| AU2006315099C1 (en) | 2013-01-10 |
| EP1951263A1 (en) | 2008-08-06 |
| AU2006315099B2 (en) | 2012-07-05 |
| US20090239816A1 (en) | 2009-09-24 |
| WO2007056829A1 (en) | 2007-05-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2630932A1 (en) | Multitargeting interfering rnas and methods of their use and design | |
| EP1670518B1 (en) | Rna interference for the treatment of gain-of-function disorders | |
| US20130245096A1 (en) | COMPOSITIONS AND METHODS FOR ACTIVATING EXPRESSION BY A SPECIFIC ENDOGENOUS miRNA | |
| KR102825946B1 (ko) | IL4Rα, TRPA1, 또는 F2RL1을 표적화하는 RNA 복합체를 사용한 아토피 피부염 및 천식의 치료 | |
| JP2005521393A (ja) | Ｈｉｖ治療 | |
| JP2014503553A (ja) | 新血管新生と関連する疾患及び状態を治療するためのｍｉＲＮＡ | |
| JPH09507502A (ja) | ｒａｆ遺伝子発現のアンチセンスオリゴヌクレオチド調節 | |
| WO2008084319A2 (ja) | 新規核酸 | |
| WO2014096418A2 (en) | Micrornas as therapeutics and biomarkers for epilepsy | |
| CN110123828A (zh) | Pralr的抑制剂在制备治疗耐紫杉醇卵巢癌的药物中的应用 | |
| US20120301449A1 (en) | Rna interference target for treating aids | |
| JP2024525868A (ja) | 産物及び組成物 | |
| CN119384283A (zh) | 使用修饰的sirna-gem剂治疗癌症的组合物和方法 | |
| EP2658973A2 (en) | siRNA FOR INHIBITION OF Hif1alpha EXPRESSION AND ANTICANCER COMPOSITION CONTAINING THE SAME | |
| JP2006526989A (ja) | 抗炎症療法としての、アンチセンス・オリゴヌクレオチドとｓｉＲＮＡを用いてアポトーシス特異的ｅＩＦ−５Ａ（“ｅＩＦ−５Ａ”）の阻害 | |
| Xia et al. | Inhibition of retinal neovascularization by siRNA targeting VEGF165 | |
| Cohen | Oligonucleotide therapeutics | |
| US20260092275A1 (en) | Products and compositions | |
| WO2021244460A1 (zh) | 口腔鳞癌相关生物标志物及诊断和治疗方法 | |
| CN110129319B (zh) | 一种PRALR的siRNA及其用途 | |
| WO2011065677A2 (ko) | 암 치료용 약학 조성물 | |
| US20040072769A1 (en) | Methods for design and selection of short double-stranded oligonucleotides, and compounds of gene drugs | |
| US7262175B2 (en) | Synthetic oligonucleotides as inducers of erythroid differentiation | |
| US20060223768A1 (en) | Regulation of gene expression | |
| WO2025139392A1 (zh) | 抑制CTGF基因表达的siRNA及其用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20141121 |