JP2017527616A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2017527616A5 JP2017527616A5 JP2017531928A JP2017531928A JP2017527616A5 JP 2017527616 A5 JP2017527616 A5 JP 2017527616A5 JP 2017531928 A JP2017531928 A JP 2017531928A JP 2017531928 A JP2017531928 A JP 2017531928A JP 2017527616 A5 JP2017527616 A5 JP 2017527616A5
- Authority
- JP
- Japan
- Prior art keywords
- nrp1
- trap
- seq
- sema3a
- domain
- 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.)
- Granted
Links
- 102000004207 Neuropilin-1 Human genes 0.000 claims description 663
- 108090000772 Neuropilin-1 Proteins 0.000 claims description 663
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 170
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 168
- 229920001184 polypeptide Polymers 0.000 claims description 165
- 210000004027 cell Anatomy 0.000 claims description 129
- 238000000034 method Methods 0.000 claims description 98
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 59
- 239000000203 mixture Substances 0.000 claims description 50
- 150000007523 nucleic acids Chemical class 0.000 claims description 47
- 206010061218 Inflammation Diseases 0.000 claims description 42
- 230000004054 inflammatory process Effects 0.000 claims description 42
- 102000039446 nucleic acids Human genes 0.000 claims description 40
- 108020004707 nucleic acids Proteins 0.000 claims description 40
- 230000004068 intracellular signaling Effects 0.000 claims description 39
- 239000013598 vector Substances 0.000 claims description 33
- 206010040047 Sepsis Diseases 0.000 claims description 29
- 108020004459 Small interfering RNA Proteins 0.000 claims description 27
- 230000001404 mediated effect Effects 0.000 claims description 25
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 22
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 22
- 230000028327 secretion Effects 0.000 claims description 21
- 102000004889 Interleukin-6 Human genes 0.000 claims description 13
- 108090001005 Interleukin-6 Proteins 0.000 claims description 13
- 230000006378 damage Effects 0.000 claims description 9
- 239000013604 expression vector Substances 0.000 claims description 6
- 210000001539 phagocyte Anatomy 0.000 claims description 6
- 208000027418 Wounds and injury Diseases 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 4
- 241000702421 Dependoparvovirus Species 0.000 claims description 3
- 108091027967 Small hairpin RNA Proteins 0.000 claims description 3
- 239000013603 viral vector Substances 0.000 claims description 3
- 239000004055 small Interfering RNA Substances 0.000 claims 1
- 108010090319 Semaphorin-3A Proteins 0.000 description 183
- 102000013008 Semaphorin-3A Human genes 0.000 description 183
- 241000699670 Mus sp. Species 0.000 description 141
- 210000001525 retina Anatomy 0.000 description 136
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 118
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 117
- 235000001014 amino acid Nutrition 0.000 description 103
- 229940024606 amino acid Drugs 0.000 description 101
- 150000001413 amino acids Chemical class 0.000 description 99
- 210000002864 mononuclear phagocyte Anatomy 0.000 description 94
- 101150051337 NRP1 gene Proteins 0.000 description 93
- 230000027455 binding Effects 0.000 description 83
- 239000003446 ligand Substances 0.000 description 67
- 230000000694 effects Effects 0.000 description 59
- 230000014509 gene expression Effects 0.000 description 59
- 210000000274 microglia Anatomy 0.000 description 57
- 241000699666 Mus <mouse, genus> Species 0.000 description 52
- 150000001875 compounds Chemical class 0.000 description 51
- 206010012689 Diabetic retinopathy Diseases 0.000 description 43
- 210000002540 macrophage Anatomy 0.000 description 43
- 230000002207 retinal effect Effects 0.000 description 40
- 208000017442 Retinal disease Diseases 0.000 description 36
- 206010038923 Retinopathy Diseases 0.000 description 36
- 230000008859 change Effects 0.000 description 35
- 230000035772 mutation Effects 0.000 description 35
- 230000002792 vascular Effects 0.000 description 35
- 108090000623 proteins and genes Proteins 0.000 description 34
- 239000012634 fragment Substances 0.000 description 33
- 230000005764 inhibitory process Effects 0.000 description 32
- 230000002401 inhibitory effect Effects 0.000 description 28
- 239000002773 nucleotide Substances 0.000 description 28
- 125000003729 nucleotide group Chemical group 0.000 description 28
- 239000003981 vehicle Substances 0.000 description 28
- 206010040070 Septic Shock Diseases 0.000 description 27
- 230000015788 innate immune response Effects 0.000 description 27
- 230000007959 normoxia Effects 0.000 description 27
- 235000018102 proteins Nutrition 0.000 description 27
- 102000004169 proteins and genes Human genes 0.000 description 27
- 230000036303 septic shock Effects 0.000 description 27
- 102000004127 Cytokines Human genes 0.000 description 26
- 108090000695 Cytokines Proteins 0.000 description 26
- 230000001419 dependent effect Effects 0.000 description 26
- 108010029485 Protein Isoforms Proteins 0.000 description 25
- 102000001708 Protein Isoforms Human genes 0.000 description 25
- 230000001965 increasing effect Effects 0.000 description 25
- 239000007924 injection Substances 0.000 description 25
- 238000002347 injection Methods 0.000 description 25
- 229910052760 oxygen Inorganic materials 0.000 description 24
- 238000011282 treatment Methods 0.000 description 24
- 210000001519 tissue Anatomy 0.000 description 23
- 206010008089 Cerebral artery occlusion Diseases 0.000 description 22
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 22
- 102100022338 Integrin alpha-M Human genes 0.000 description 22
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 22
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 22
- 210000002798 bone marrow cell Anatomy 0.000 description 22
- 108020004999 messenger RNA Proteins 0.000 description 22
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 22
- 239000001301 oxygen Substances 0.000 description 22
- 238000006467 substitution reaction Methods 0.000 description 22
- 230000033115 angiogenesis Effects 0.000 description 21
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 21
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 20
- 208000006011 Stroke Diseases 0.000 description 20
- 230000000692 anti-sense effect Effects 0.000 description 20
- 230000000302 ischemic effect Effects 0.000 description 20
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 19
- 238000004519 manufacturing process Methods 0.000 description 19
- 239000002609 medium Substances 0.000 description 19
- 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 18
- 210000004556 brain Anatomy 0.000 description 18
- 206010012601 diabetes mellitus Diseases 0.000 description 18
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 18
- 230000000770 proinflammatory effect Effects 0.000 description 18
- 210000001185 bone marrow Anatomy 0.000 description 17
- 102000005962 receptors Human genes 0.000 description 17
- 108020003175 receptors Proteins 0.000 description 17
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 16
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 15
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 15
- 238000003776 cleavage reaction Methods 0.000 description 15
- 230000009368 gene silencing by RNA Effects 0.000 description 15
- 102000058223 human VEGFA Human genes 0.000 description 15
- 208000027866 inflammatory disease Diseases 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 230000007017 scission Effects 0.000 description 15
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 238000001727 in vivo Methods 0.000 description 14
- 230000035699 permeability Effects 0.000 description 14
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 13
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 230000002950 deficient Effects 0.000 description 13
- 238000012217 deletion Methods 0.000 description 13
- 230000037430 deletion Effects 0.000 description 13
- 238000010586 diagram Methods 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 230000001575 pathological effect Effects 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 12
- 201000006474 Brain Ischemia Diseases 0.000 description 12
- 206010008120 Cerebral ischaemia Diseases 0.000 description 12
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 12
- 108091034117 Oligonucleotide Proteins 0.000 description 12
- 108091005804 Peptidases Proteins 0.000 description 12
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 206010008118 cerebral infarction Diseases 0.000 description 12
- 210000003161 choroid Anatomy 0.000 description 12
- 229910052731 fluorine Inorganic materials 0.000 description 12
- 229910052740 iodine Inorganic materials 0.000 description 12
- 125000005647 linker group Chemical group 0.000 description 12
- 238000010172 mouse model Methods 0.000 description 12
- 230000002265 prevention Effects 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 12
- 125000000539 amino acid group Chemical group 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 238000000338 in vitro Methods 0.000 description 11
- 239000002502 liposome Substances 0.000 description 11
- 210000004185 liver Anatomy 0.000 description 11
- 208000002780 macular degeneration Diseases 0.000 description 11
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 10
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 10
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 10
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 description 10
- 101000577540 Homo sapiens Neuropilin-1 Proteins 0.000 description 10
- 206010038934 Retinopathy proliferative Diseases 0.000 description 10
- 206010064930 age-related macular degeneration Diseases 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 230000006698 induction Effects 0.000 description 10
- 230000008728 vascular permeability Effects 0.000 description 10
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 9
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 9
- 108090001090 Lectins Proteins 0.000 description 9
- 102000004856 Lectins Human genes 0.000 description 9
- 102000014105 Semaphorin Human genes 0.000 description 9
- 108050003978 Semaphorin Proteins 0.000 description 9
- 230000004913 activation Effects 0.000 description 9
- 230000007850 degeneration Effects 0.000 description 9
- 210000003734 kidney Anatomy 0.000 description 9
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 230000009885 systemic effect Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 8
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 8
- 101100133721 Caenorhabditis elegans npr-1 gene Proteins 0.000 description 8
- 208000024248 Vascular System injury Diseases 0.000 description 8
- 208000012339 Vascular injury Diseases 0.000 description 8
- 238000009825 accumulation Methods 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000016396 cytokine production Effects 0.000 description 8
- 229960003699 evans blue Drugs 0.000 description 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 8
- 230000001771 impaired effect Effects 0.000 description 8
- 230000002757 inflammatory effect Effects 0.000 description 8
- 210000002569 neuron Anatomy 0.000 description 8
- 230000011664 signaling Effects 0.000 description 8
- 238000010186 staining Methods 0.000 description 8
- 238000001356 surgical procedure Methods 0.000 description 8
- 208000024827 Alzheimer disease Diseases 0.000 description 7
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 7
- 206010061216 Infarction Diseases 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- 102000002111 Neuropilin Human genes 0.000 description 7
- 108050009450 Neuropilin Proteins 0.000 description 7
- 206010030113 Oedema Diseases 0.000 description 7
- 238000011529 RT qPCR Methods 0.000 description 7
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 7
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 7
- 230000002491 angiogenic effect Effects 0.000 description 7
- 206010003246 arthritis Diseases 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 7
- 230000002490 cerebral effect Effects 0.000 description 7
- 230000035605 chemotaxis Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 230000007574 infarction Effects 0.000 description 7
- 238000011813 knockout mouse model Methods 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 210000004379 membrane Anatomy 0.000 description 7
- 201000006417 multiple sclerosis Diseases 0.000 description 7
- 230000001537 neural effect Effects 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 102000040430 polynucleotide Human genes 0.000 description 7
- 108091033319 polynucleotide Proteins 0.000 description 7
- 239000002157 polynucleotide Substances 0.000 description 7
- 238000003753 real-time PCR Methods 0.000 description 7
- 210000000952 spleen Anatomy 0.000 description 7
- 229960001052 streptozocin Drugs 0.000 description 7
- 108010085238 Actins Proteins 0.000 description 6
- 102000007469 Actins Human genes 0.000 description 6
- 201000004624 Dermatitis Diseases 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- 102000035195 Peptidases Human genes 0.000 description 6
- 239000004365 Protease Substances 0.000 description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 description 6
- 208000007135 Retinal Neovascularization Diseases 0.000 description 6
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 6
- 108010076818 TEV protease Proteins 0.000 description 6
- 206010046851 Uveitis Diseases 0.000 description 6
- 230000007000 age related cognitive decline Effects 0.000 description 6
- 210000001168 carotid artery common Anatomy 0.000 description 6
- 230000036755 cellular response Effects 0.000 description 6
- 238000006471 dimerization reaction Methods 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000008595 infiltration Effects 0.000 description 6
- 238000001764 infiltration Methods 0.000 description 6
- 230000000670 limiting effect Effects 0.000 description 6
- 230000000926 neurological effect Effects 0.000 description 6
- 238000006386 neutralization reaction Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 235000019833 protease Nutrition 0.000 description 6
- 235000019419 proteases Nutrition 0.000 description 6
- 238000011002 quantification Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 206010029113 Neovascularisation Diseases 0.000 description 5
- 208000028389 Nerve injury Diseases 0.000 description 5
- 102100028762 Neuropilin-1 Human genes 0.000 description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 235000004279 alanine Nutrition 0.000 description 5
- 230000003698 anagen phase Effects 0.000 description 5
- 235000003704 aspartic acid Nutrition 0.000 description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 229960002286 clodronic acid Drugs 0.000 description 5
- 230000003436 cytoskeletal effect Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 235000013922 glutamic acid Nutrition 0.000 description 5
- 239000004220 glutamic acid Substances 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 238000007912 intraperitoneal administration Methods 0.000 description 5
- 229960002725 isoflurane Drugs 0.000 description 5
- 238000000370 laser capture micro-dissection Methods 0.000 description 5
- 230000005012 migration Effects 0.000 description 5
- 238000013508 migration Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000008764 nerve damage Effects 0.000 description 5
- 210000003024 peritoneal macrophage Anatomy 0.000 description 5
- 229910052698 phosphorus Inorganic materials 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 230000007115 recruitment Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 230000000451 tissue damage Effects 0.000 description 5
- 231100000827 tissue damage Toxicity 0.000 description 5
- 231100000216 vascular lesion Toxicity 0.000 description 5
- 102100040121 Allograft inflammatory factor 1 Human genes 0.000 description 4
- 102100039339 Atrial natriuretic peptide receptor 1 Human genes 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 108090000994 Catalytic RNA Proteins 0.000 description 4
- 102000053642 Catalytic RNA Human genes 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 4
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 4
- 206010061818 Disease progression Diseases 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 101000890626 Homo sapiens Allograft inflammatory factor 1 Proteins 0.000 description 4
- 101000961044 Homo sapiens Atrial natriuretic peptide receptor 1 Proteins 0.000 description 4
- 102100034343 Integrase Human genes 0.000 description 4
- 208000001344 Macular Edema Diseases 0.000 description 4
- 206010025415 Macular oedema Diseases 0.000 description 4
- 101100349097 Mus musculus Nrp1 gene Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
- 239000000074 antisense oligonucleotide Substances 0.000 description 4
- 238000012230 antisense oligonucleotides Methods 0.000 description 4
- 230000004888 barrier function Effects 0.000 description 4
- 238000005452 bending Methods 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 210000004155 blood-retinal barrier Anatomy 0.000 description 4
- 230000004378 blood-retinal barrier Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 239000012228 culture supernatant Substances 0.000 description 4
- 230000005750 disease progression Effects 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- -1 host cell Chemical class 0.000 description 4
- 102000050920 human NRP1 Human genes 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000007928 intraperitoneal injection Substances 0.000 description 4
- 230000009545 invasion Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 201000010230 macular retinal edema Diseases 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 238000010232 migration assay Methods 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000001742 protein purification Methods 0.000 description 4
- 230000000250 revascularization Effects 0.000 description 4
- 108091092562 ribozyme Proteins 0.000 description 4
- 239000011435 rock Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000002864 sequence alignment Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 230000009261 transgenic effect Effects 0.000 description 4
- 210000005166 vasculature Anatomy 0.000 description 4
- 210000004127 vitreous body Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- 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 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 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 3
- 208000001351 Epiretinal Membrane Diseases 0.000 description 3
- 206010015866 Extravasation Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000632261 Homo sapiens Semaphorin-3A Proteins 0.000 description 3
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- 208000031471 Macular fibrosis Diseases 0.000 description 3
- 101000713935 Mus musculus Tudor domain-containing protein 7 Proteins 0.000 description 3
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 3
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- 102000009203 Sema domains Human genes 0.000 description 3
- 108050000099 Sema domains Proteins 0.000 description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 3
- ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- WZSDNEJJUSYNSG-UHFFFAOYSA-N azocan-1-yl-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCCCCCC2)=C1 WZSDNEJJUSYNSG-UHFFFAOYSA-N 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000005754 cellular signaling Effects 0.000 description 3
- 239000002975 chemoattractant Substances 0.000 description 3
- 230000003399 chemotactic effect Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000036251 extravasation Effects 0.000 description 3
- 239000003889 eye drop Substances 0.000 description 3
- 229940012356 eye drops Drugs 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000003447 ipsilateral effect Effects 0.000 description 3
- 239000002523 lectin Substances 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 230000022275 macrophage chemotaxis Effects 0.000 description 3
- 231100000682 maximum tolerated dose Toxicity 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000004088 microvessel Anatomy 0.000 description 3
- 210000003657 middle cerebral artery Anatomy 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 150000004713 phosphodiesters Chemical class 0.000 description 3
- 230000006461 physiological response Effects 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000003994 retinal ganglion cell Anatomy 0.000 description 3
- 238000010839 reverse transcription Methods 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 230000006459 vascular development Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- IDDDVXIUIXWAGJ-DDSAHXNVSA-N 4-[(1r)-1-aminoethyl]-n-pyridin-4-ylcyclohexane-1-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H](N)C)CCC1C(=O)NC1=CC=NC=C1 IDDDVXIUIXWAGJ-DDSAHXNVSA-N 0.000 description 2
- 206010002329 Aneurysm Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102100026735 Coagulation factor VIII Human genes 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- 101150026192 Crb1 gene Proteins 0.000 description 2
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 208000003098 Ganglion Cysts Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 101100495074 Mus musculus Ccl2 gene Proteins 0.000 description 2
- 101100007778 Mus musculus Crb1 gene Proteins 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 108091005461 Nucleic proteins Chemical group 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 208000002367 Retinal Perforations Diseases 0.000 description 2
- 206010057430 Retinal injury Diseases 0.000 description 2
- 108010057163 Ribonuclease III Proteins 0.000 description 2
- 102000003661 Ribonuclease III Human genes 0.000 description 2
- 108010085603 SFLLRNPND Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 208000005400 Synovial Cyst Diseases 0.000 description 2
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 208000038016 acute inflammation Diseases 0.000 description 2
- 230000006022 acute inflammation Effects 0.000 description 2
- 230000010398 acute inflammatory response Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 108010004469 allophycocyanin Proteins 0.000 description 2
- 238000002583 angiography Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000005667 attractant Substances 0.000 description 2
- 230000004009 axon guidance Effects 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000034303 cell budding Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000004581 coalescence Methods 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000037416 cystogenesis Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 230000004438 eyesight Effects 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
- 210000003194 forelimb Anatomy 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 102000057183 human SEMA3A Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000006882 induction of apoptosis Effects 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 230000006749 inflammatory damage Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000017306 interleukin-6 production Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 208000029233 macular holes Diseases 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- 230000001617 migratory effect Effects 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 230000007472 neurodevelopment Effects 0.000 description 2
- 230000003959 neuroinflammation Effects 0.000 description 2
- 230000002314 neuroinflammatory effect Effects 0.000 description 2
- 210000002445 nipple Anatomy 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 210000003200 peritoneal cavity Anatomy 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 108091008695 photoreceptors Proteins 0.000 description 2
- 229920002647 polyamide Polymers 0.000 description 2
- 229920002704 polyhistidine Polymers 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000001023 pro-angiogenic effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 230000004263 retinal angiogenesis Effects 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000009732 tufting Methods 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 230000006433 tumor necrosis factor production Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 1
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-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
- 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 group 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
- 229920000936 Agarose Polymers 0.000 description 1
- 239000012117 Alexa Fluor 700 Substances 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 1
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 1
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 1
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 238000011814 C57BL/6N mouse Methods 0.000 description 1
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 1
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 1
- 101100204059 Caenorhabditis elegans trap-2 gene Proteins 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- LTLYEAJONXGNFG-DCAQKATOSA-N E64 Chemical compound NC(=N)NCCCCNC(=O)[C@H](CC(C)C)NC(=O)[C@H]1O[C@@H]1C(O)=O LTLYEAJONXGNFG-DCAQKATOSA-N 0.000 description 1
- 102100030013 Endoribonuclease Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 102000011652 Formyl peptide receptors Human genes 0.000 description 1
- 108010076288 Formyl peptide receptors Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000219774 Griffonia Species 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101001010783 Homo sapiens Endoribonuclease Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101000582320 Homo sapiens Neurogenic differentiation factor 6 Proteins 0.000 description 1
- 101000654674 Homo sapiens Semaphorin-6A Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 206010058490 Hyperoxia Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 101710197072 Lectin 1 Proteins 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101001065556 Mus musculus Lymphocyte antigen 6G Proteins 0.000 description 1
- MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 102000009065 Netrin-1 Human genes 0.000 description 1
- 108010074223 Netrin-1 Proteins 0.000 description 1
- 102100030589 Neurogenic differentiation factor 6 Human genes 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102100028492 Neuropilin-2 Human genes 0.000 description 1
- 108090000770 Neuropilin-2 Proteins 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 238000013355 OIR mouse model Methods 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 102000000536 PPAR gamma Human genes 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 241000577979 Peromyscus spicilegus Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920000153 Povidone-iodine Polymers 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 101150111584 RHOA gene Proteins 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 101100080536 Rattus norvegicus Nrp1 gene Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 102100027974 Semaphorin-3A Human genes 0.000 description 1
- 101710199445 Semaphorin-3F Proteins 0.000 description 1
- 102100027751 Semaphorin-3F Human genes 0.000 description 1
- 102100032795 Semaphorin-6A Human genes 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000034698 Vitreous haemorrhage Diseases 0.000 description 1
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 238000002835 absorbance Methods 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
- 239000004480 active ingredient Substances 0.000 description 1
- MGSKVZWGBWPBTF-UHFFFAOYSA-N aebsf Chemical compound NCCC1=CC=C(S(F)(=O)=O)C=C1 MGSKVZWGBWPBTF-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 239000011717 all-trans-retinol Substances 0.000 description 1
- 235000019169 all-trans-retinol Nutrition 0.000 description 1
- 125000005122 aminoalkylamino group Chemical group 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000015624 blood vessel development Effects 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000004640 cellular pathway Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- HJKBJIYDJLVSAO-UHFFFAOYSA-L clodronic acid disodium salt Chemical compound [Na+].[Na+].OP([O-])(=O)C(Cl)(Cl)P(O)([O-])=O HJKBJIYDJLVSAO-UHFFFAOYSA-L 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001427 coherent effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 201000011190 diabetic macular edema Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000004459 forage Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000037417 hyperactivation Effects 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 230000000222 hyperoxic effect Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 230000019189 interleukin-1 beta production Effects 0.000 description 1
- 238000010212 intracellular staining Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- OOYGSFOGFJDDHP-KMCOLRRFSA-N kanamycin A sulfate Chemical group OS(O)(=O)=O.O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N OOYGSFOGFJDDHP-KMCOLRRFSA-N 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- YFCUZWYIPBUQBD-ZOWNYOTGSA-N n-[(3s)-7-amino-1-chloro-2-oxoheptan-3-yl]-4-methylbenzenesulfonamide;hydron;chloride Chemical compound Cl.CC1=CC=C(S(=O)(=O)N[C@@H](CCCCN)C(=O)CCl)C=C1 YFCUZWYIPBUQBD-ZOWNYOTGSA-N 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 230000003988 neural development Effects 0.000 description 1
- 210000005157 neural retina Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 238000012014 optical coherence tomography Methods 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- VYNDHICBIRRPFP-UHFFFAOYSA-N pacific blue Chemical compound FC1=C(O)C(F)=C2OC(=O)C(C(=O)O)=CC2=C1 VYNDHICBIRRPFP-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000000649 photocoagulation Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 102000002022 plexin Human genes 0.000 description 1
- 108050009312 plexin Proteins 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000032361 posttranscriptional gene silencing Effects 0.000 description 1
- 229960001621 povidone-iodine Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 101150059999 pro gene Proteins 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 125000006853 reporter group Chemical group 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 210000001116 retinal neuron Anatomy 0.000 description 1
- 230000004250 retinal swelling Effects 0.000 description 1
- 230000004233 retinal vasculature Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003354 serine derivatives Chemical class 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 108010063955 thrombin receptor peptide (42-47) Proteins 0.000 description 1
- 210000002262 tip cell Anatomy 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009752 translational inhibition Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000006453 vascular barrier function Effects 0.000 description 1
- 230000006711 vascular endothelial growth factor production Effects 0.000 description 1
- 230000006426 vascular sprouting Effects 0.000 description 1
- 230000007998 vessel formation Effects 0.000 description 1
- 230000004382 visual function Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 208000000318 vitreous detachment Diseases 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462046459P | 2014-09-05 | 2014-09-05 | |
| US62/046,459 | 2014-09-05 | ||
| PCT/CA2015/050862 WO2016033699A1 (en) | 2014-09-05 | 2015-09-08 | Compositions and methods for treating and preventing inflammation |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020070982A Division JP7194146B2 (ja) | 2014-09-05 | 2020-04-10 | 炎症を処置および予防するための組成物および方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017527616A JP2017527616A (ja) | 2017-09-21 |
| JP2017527616A5 true JP2017527616A5 (enExample) | 2018-10-18 |
| JP6692816B2 JP6692816B2 (ja) | 2020-05-13 |
Family
ID=55438956
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017531928A Active JP6692816B2 (ja) | 2014-09-05 | 2015-09-08 | 炎症を処置および予防するための組成物および方法 |
| JP2020070982A Active JP7194146B2 (ja) | 2014-09-05 | 2020-04-10 | 炎症を処置および予防するための組成物および方法 |
| JP2022196745A Pending JP2023022308A (ja) | 2014-09-05 | 2022-12-09 | 炎症を処置および予防するための組成物および方法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020070982A Active JP7194146B2 (ja) | 2014-09-05 | 2020-04-10 | 炎症を処置および予防するための組成物および方法 |
| JP2022196745A Pending JP2023022308A (ja) | 2014-09-05 | 2022-12-09 | 炎症を処置および予防するための組成物および方法 |
Country Status (17)
| Country | Link |
|---|---|
| US (4) | US10738122B2 (enExample) |
| EP (1) | EP3189074B1 (enExample) |
| JP (3) | JP6692816B2 (enExample) |
| KR (2) | KR102696275B1 (enExample) |
| CN (2) | CN113980116A (enExample) |
| AU (1) | AU2015311563B2 (enExample) |
| CA (1) | CA2960054C (enExample) |
| DK (1) | DK3189074T3 (enExample) |
| ES (1) | ES2865488T3 (enExample) |
| HR (1) | HRP20210577T1 (enExample) |
| HU (1) | HUE054204T2 (enExample) |
| LT (1) | LT3189074T (enExample) |
| PL (1) | PL3189074T3 (enExample) |
| PT (1) | PT3189074T (enExample) |
| RS (1) | RS61703B1 (enExample) |
| SI (1) | SI3189074T1 (enExample) |
| WO (1) | WO2016033699A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6437462B2 (ja) | 2013-02-21 | 2018-12-12 | アールエスイーエム・リミテッド・パートナーシップ | 眼内透過性亢進の予防及び治療におけるsema3aの阻害 |
| WO2016033699A1 (en) | 2014-09-05 | 2016-03-10 | Rsem, Limited Partnership | Compositions and methods for treating and preventing inflammation |
| DK3353196T5 (da) * | 2015-09-22 | 2024-09-30 | Inst Nat Sante Rech Med | Polypeptider, der er i stand til at inhibere bindingen mellem leptin og neuropilin-1 |
| US20200056186A1 (en) * | 2016-09-22 | 2020-02-20 | Rsem, Limited Partnership | Compositions comprising sasp modulators and senescence attenuators and uses thereof for modulating cellular senescence |
| US20190330640A1 (en) * | 2017-01-09 | 2019-10-31 | Secarna Pharmaceuticals Gmbh & Co. Kg | Oligonucleotides inhibiting the expression of nrp1 |
| CN110290785A (zh) * | 2017-03-08 | 2019-09-27 | 日清奥利友集团株式会社 | 抗炎症剂、抗炎症用药物组合物、抗炎症用食品组合物 |
| JOP20210300A1 (ar) * | 2019-05-09 | 2023-01-30 | Boehringer Ingelheim Int | أجسام مضادة مضادة لسيما 3أ واستخداماتها في علاج أمراض العين أو البصر |
| TWI865542B (zh) | 2019-06-12 | 2024-12-11 | 瑞士商諾華公司 | 利鈉肽受體1抗體及使用方法 |
| TWI859339B (zh) * | 2019-09-24 | 2024-10-21 | 德商百靈佳殷格翰國際股份有限公司 | 抗nrp1a抗體及其用於治療眼或眼部疾病之用途 |
| CN112641928A (zh) * | 2019-10-11 | 2021-04-13 | 田中纯美 | 一种用于血管新生、淋巴管新生相关疾病的多肽及其用途 |
| EP4157312A4 (en) * | 2020-05-27 | 2024-07-31 | Baylor College of Medicine | COMPOSITIONS AND METHODS FOR TREATING NEOVASCULARIZATION AND ISCHEMIC RETINOPATHIES BY TARGETING ANGIOGENESIS AND CHOLESTEROL TRANSPORT |
| WO2021258218A1 (en) * | 2020-06-26 | 2021-12-30 | Semathera Inc. | Use of soluble nrp1 polypeptides for the treatment of coronavirus infections |
| US20230312684A1 (en) * | 2020-07-31 | 2023-10-05 | Pinetree Therapeutics, Inc. | Neuropilin and angiotensin converting enzyme 2 fusion peptides for treating viral infections |
| CN118201628A (zh) | 2021-09-08 | 2024-06-14 | 斯特拉斯堡大学 | 丛蛋白a1的跨膜肽拮抗剂及其治疗应用 |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US4806463A (en) | 1986-05-23 | 1989-02-21 | Worcester Foundation For Experimental Biology | Inhibition of HTLV-III by exogenous oligonucleotides |
| US5194428A (en) | 1986-05-23 | 1993-03-16 | Worcester Foundation For Experimental Biology | Inhibition of influenza virus replication by oligonucleotide phosphorothioates |
| US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US5004810A (en) | 1988-09-30 | 1991-04-02 | Schering Corporation | Antiviral oligomers |
| US5098890A (en) | 1988-11-07 | 1992-03-24 | Temple University-Of The Commonwealth System Of Higher Education | Antisence oligonucleotides to c-myb proto-oncogene and uses thereof |
| US5087617A (en) | 1989-02-15 | 1992-02-11 | Board Of Regents, The University Of Texas System | Methods and compositions for treatment of cancer using oligonucleotides |
| US5166195A (en) | 1990-05-11 | 1992-11-24 | Isis Pharmaceuticals, Inc. | Antisense inhibitors of the human immunodeficiency virus phosphorothioate oligonucleotides |
| US5135917A (en) | 1990-07-12 | 1992-08-04 | Nova Pharmaceutical Corporation | Interleukin receptor expression inhibiting antisense oligonucleotides |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| AUPM516994A0 (en) | 1994-04-20 | 1994-05-12 | Gene Shears Pty. Limited | An in vivo gene expression system |
| US20020132788A1 (en) | 2000-11-06 | 2002-09-19 | David Lewis | Inhibition of gene expression by delivery of small interfering RNA to post-embryonic animal cells in vivo |
| US20020173478A1 (en) | 2000-11-14 | 2002-11-21 | The Trustees Of The University Of Pennsylvania | Post-transcriptional gene silencing by RNAi in mammalian cells |
| EP1418834A4 (en) | 2001-07-20 | 2007-04-04 | Sinai School Medicine | METHOD FOR DIAGNOSIS AND TREATMENT OF ALZHEIMER DISEASE AND PARKINSON DISEASE |
| EP1429801A1 (en) | 2001-09-26 | 2004-06-23 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Neuropilin as a novel therapeutic target for modulation of immune reponses |
| EP1439192A1 (en) * | 2003-01-15 | 2004-07-21 | Xerion Pharmaceuticals AG | Neuropilin-1 inhibitors |
| AU2006267097A1 (en) | 2005-07-13 | 2007-01-18 | Beth Israel Deaconess Medical Center | Methods of diagnosing and treating an inflammatory response |
| UA96139C2 (uk) * | 2005-11-08 | 2011-10-10 | Дженентек, Інк. | Антитіло до нейропіліну-1 (nrp1) |
| MX2009012282A (es) | 2007-05-17 | 2009-11-25 | Genentech Inc | Estructuras cristalinas de fragmentos de neuropilina y complejos de neuropilina-anticuerpos. |
| CN103193888B (zh) * | 2007-05-17 | 2015-09-09 | 健泰科生物技术公司 | 神经毡蛋白片段与神经毡蛋白抗体复合物的晶体结构 |
| WO2009060159A1 (en) | 2007-11-08 | 2009-05-14 | Medigene Limited | Mutated ilt molecules |
| EP3275898B1 (en) * | 2009-11-05 | 2024-06-05 | Osaka University | Therapeutic agent for autoimmune diseases or allergy, and method for screening for the therapeutic agent |
| EP2613773A2 (en) * | 2010-09-09 | 2013-07-17 | Trifoilium ApS | Airway administration of angiogenesis inhibitors |
| ES2728854T3 (es) | 2013-02-06 | 2019-10-29 | Univ Yokohama City | Anticuerpo anti-semaforina 3A y tratamiento de enfermedad de Alzheimer y enfermedades inmunitarias inflamatorias usando el mismo |
| JP6437462B2 (ja) | 2013-02-21 | 2018-12-12 | アールエスイーエム・リミテッド・パートナーシップ | 眼内透過性亢進の予防及び治療におけるsema3aの阻害 |
| WO2016033699A1 (en) | 2014-09-05 | 2016-03-10 | Rsem, Limited Partnership | Compositions and methods for treating and preventing inflammation |
-
2015
- 2015-09-08 WO PCT/CA2015/050862 patent/WO2016033699A1/en not_active Ceased
- 2015-09-08 CA CA2960054A patent/CA2960054C/en active Active
- 2015-09-08 KR KR1020177007655A patent/KR102696275B1/ko active Active
- 2015-09-08 JP JP2017531928A patent/JP6692816B2/ja active Active
- 2015-09-08 AU AU2015311563A patent/AU2015311563B2/en active Active
- 2015-09-08 PL PL15838150T patent/PL3189074T3/pl unknown
- 2015-09-08 ES ES15838150T patent/ES2865488T3/es active Active
- 2015-09-08 SI SI201531572T patent/SI3189074T1/sl unknown
- 2015-09-08 KR KR1020247027036A patent/KR102869487B1/ko active Active
- 2015-09-08 LT LTEP15838150.9T patent/LT3189074T/lt unknown
- 2015-09-08 CN CN202111209393.3A patent/CN113980116A/zh active Pending
- 2015-09-08 RS RS20210437A patent/RS61703B1/sr unknown
- 2015-09-08 CN CN201580058020.7A patent/CN107207577B/zh active Active
- 2015-09-08 US US15/507,407 patent/US10738122B2/en active Active
- 2015-09-08 DK DK15838150.9T patent/DK3189074T3/da active
- 2015-09-08 PT PT158381509T patent/PT3189074T/pt unknown
- 2015-09-08 EP EP15838150.9A patent/EP3189074B1/en active Active
- 2015-09-08 HR HRP20210577TT patent/HRP20210577T1/hr unknown
- 2015-09-08 HU HUE15838150A patent/HUE054204T2/hu unknown
-
2019
- 2019-05-24 US US16/422,273 patent/US10766964B2/en active Active
-
2020
- 2020-04-10 JP JP2020070982A patent/JP7194146B2/ja active Active
- 2020-08-03 US US16/983,185 patent/US11649292B2/en active Active
-
2022
- 2022-12-09 JP JP2022196745A patent/JP2023022308A/ja active Pending
-
2023
- 2023-03-23 US US18/188,707 patent/US20230265199A1/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7194146B2 (ja) | 炎症を処置および予防するための組成物および方法 | |
| JP2017527616A5 (enExample) | ||
| Dejda et al. | Neuropilin-1 mediates myeloid cell chemoattraction and influences retinal neuroimmune crosstalk | |
| CN110023332B (zh) | 包含sasp调节剂和衰老衰减剂的组合物及其用于调节细胞衰老的用途 | |
| US11268097B2 (en) | Inhibition of SEMA3A in the prevention and treatment of ocular hyperpermeability | |
| JP6689484B2 (ja) | 網膜炎症の治療において使用するための薬剤 | |
| JP2024038469A (ja) | インフラマソームの活性化を阻害するためのcd59 | |
| HK1238571A1 (en) | Compositions and methods for treating and preventing inflammation | |
| HK1238571B (en) | Compositions and methods for treating and preventing inflammation | |
| Leaderer | Development of Novel Therapeutics for the Treatment of Age-related Macular Degeneration |