CA2267833A1 - Nouveaux complexes polymeriques pour la transfection d'acides nucleiques, avec des residus destabilisant des membranes cellulaires - Google Patents
Nouveaux complexes polymeriques pour la transfection d'acides nucleiques, avec des residus destabilisant des membranes cellulaires Download PDFInfo
- Publication number
- CA2267833A1 CA2267833A1 CA002267833A CA2267833A CA2267833A1 CA 2267833 A1 CA2267833 A1 CA 2267833A1 CA 002267833 A CA002267833 A CA 002267833A CA 2267833 A CA2267833 A CA 2267833A CA 2267833 A1 CA2267833 A1 CA 2267833A1
- Authority
- CA
- Canada
- Prior art keywords
- residues
- free
- aforesaid
- functions
- polymer
- 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
- 210000000170 cell membrane Anatomy 0.000 title claims abstract description 85
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 68
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 68
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 68
- 238000001890 transfection Methods 0.000 title claims description 27
- 229920000642 polymer Polymers 0.000 claims abstract description 155
- 230000006870 function Effects 0.000 claims abstract description 120
- 239000000178 monomer Substances 0.000 claims abstract description 81
- 239000012528 membrane Substances 0.000 claims abstract description 56
- 239000002253 acid Substances 0.000 claims abstract description 51
- 102000006240 membrane receptors Human genes 0.000 claims abstract description 44
- 108020004084 membrane receptors Proteins 0.000 claims abstract description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 20
- 230000012202 endocytosis Effects 0.000 claims abstract description 14
- 210000001163 endosome Anatomy 0.000 claims abstract description 9
- 125000000524 functional group Chemical group 0.000 claims abstract description 9
- 108010039918 Polylysine Proteins 0.000 claims description 153
- 229920000656 polylysine Polymers 0.000 claims description 153
- 210000004027 cell Anatomy 0.000 claims description 110
- 230000001687 destabilization Effects 0.000 claims description 74
- 108090000623 proteins and genes Proteins 0.000 claims description 57
- 239000002609 medium Substances 0.000 claims description 49
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 46
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 37
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 34
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 27
- 230000009467 reduction Effects 0.000 claims description 27
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 26
- 238000006467 substitution reaction Methods 0.000 claims description 25
- 102000005962 receptors Human genes 0.000 claims description 23
- 108020003175 receptors Proteins 0.000 claims description 23
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 19
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 19
- 230000007935 neutral effect Effects 0.000 claims description 19
- 239000013612 plasmid Substances 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 235000018977 lysine Nutrition 0.000 claims description 17
- 230000002378 acidificating effect Effects 0.000 claims description 15
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 14
- 230000001413 cellular effect Effects 0.000 claims description 14
- 238000012546 transfer Methods 0.000 claims description 14
- 108060001084 Luciferase Proteins 0.000 claims description 13
- 239000004472 Lysine Substances 0.000 claims description 12
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 12
- 239000012736 aqueous medium Substances 0.000 claims description 12
- 238000010494 dissociation reaction Methods 0.000 claims description 12
- 230000005593 dissociations Effects 0.000 claims description 12
- PRJKNHOMHKJCEJ-UHFFFAOYSA-N imidazole-4-acetic acid Natural products OC(=O)CC1=CN=CN1 PRJKNHOMHKJCEJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000003446 ligand Substances 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 238000000338 in vitro Methods 0.000 claims description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 239000005089 Luciferase Substances 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 8
- 210000000172 cytosol Anatomy 0.000 claims description 8
- 150000002460 imidazoles Chemical class 0.000 claims description 8
- 210000004940 nucleus Anatomy 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 235000001968 nicotinic acid Nutrition 0.000 claims description 7
- 229960003512 nicotinic acid Drugs 0.000 claims description 7
- 239000011664 nicotinic acid Substances 0.000 claims description 7
- XXLFLUJXWKXUGS-UHFFFAOYSA-N 6-methoxyquinoline-4-carboxylic acid Chemical compound N1=CC=C(C(O)=O)C2=CC(OC)=CC=C21 XXLFLUJXWKXUGS-UHFFFAOYSA-N 0.000 claims description 6
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 6
- 108090001090 Lectins Proteins 0.000 claims description 6
- 102000004856 Lectins Human genes 0.000 claims description 6
- 239000005557 antagonist Substances 0.000 claims description 6
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N biotin Natural products N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 6
- 230000002950 deficient Effects 0.000 claims description 6
- 239000002523 lectin Substances 0.000 claims description 6
- 238000006116 polymerization reaction Methods 0.000 claims description 6
- 235000018102 proteins Nutrition 0.000 claims description 6
- 102000004169 proteins and genes Human genes 0.000 claims description 6
- 230000003612 virological effect Effects 0.000 claims description 6
- 238000001727 in vivo Methods 0.000 claims description 5
- 229920001184 polypeptide Polymers 0.000 claims description 5
- INDBQLZJXZLFIT-UHFFFAOYSA-N primaquine Chemical compound N1=CC=CC2=CC(OC)=CC(NC(C)CCCN)=C21 INDBQLZJXZLFIT-UHFFFAOYSA-N 0.000 claims description 5
- 102100036664 Adenosine deaminase Human genes 0.000 claims description 4
- 108010002913 Asialoglycoproteins Proteins 0.000 claims description 4
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 claims description 4
- PNIWLNAGKUGXDO-UHFFFAOYSA-N Lactosamine Natural products OC1C(N)C(O)OC(CO)C1OC1C(O)C(O)C(O)C(CO)O1 PNIWLNAGKUGXDO-UHFFFAOYSA-N 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 229960002685 biotin Drugs 0.000 claims description 4
- 235000020958 biotin Nutrition 0.000 claims description 4
- 239000011616 biotin Substances 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 210000004443 dendritic cell Anatomy 0.000 claims description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 4
- DOVBXGDYENZJBJ-ONMPCKGSSA-N lactosamine Chemical compound O=C[C@H](N)[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O DOVBXGDYENZJBJ-ONMPCKGSSA-N 0.000 claims description 4
- 239000003550 marker Substances 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229960005486 vaccine Drugs 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- KYWMCFOWDYFYLV-UHFFFAOYSA-N 1h-imidazole-2-carboxylic acid Chemical compound OC(=O)C1=NC=CN1 KYWMCFOWDYFYLV-UHFFFAOYSA-N 0.000 claims description 3
- GYEDIFVVTRKXHP-UHFFFAOYSA-N 4-n-(7-chloroquinolin-4-yl)pentane-1,4-diamine Chemical compound ClC1=CC=C2C(NC(CCCN)C)=CC=NC2=C1 GYEDIFVVTRKXHP-UHFFFAOYSA-N 0.000 claims description 3
- JOAQINSXLLMRCV-UHFFFAOYSA-N 4-{[(2-amino-4-hydroxypteridin-6-yl)methyl]amino}benzoic acid Chemical compound C1=NC2=NC(N)=NC(O)=C2N=C1CNC1=CC=C(C(O)=O)C=C1 JOAQINSXLLMRCV-UHFFFAOYSA-N 0.000 claims description 3
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 claims description 3
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
- 102000015689 E-Selectin Human genes 0.000 claims description 3
- 108010024212 E-Selectin Proteins 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- 102000008212 P-Selectin Human genes 0.000 claims description 3
- 108010035766 P-Selectin Proteins 0.000 claims description 3
- 229920006317 cationic polymer Polymers 0.000 claims description 3
- 239000012634 fragment Substances 0.000 claims description 3
- 239000003102 growth factor Substances 0.000 claims description 3
- 229960001340 histamine Drugs 0.000 claims description 3
- 239000002207 metabolite Substances 0.000 claims description 3
- GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 claims description 3
- 241000712461 unidentified influenza virus Species 0.000 claims description 3
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 claims description 2
- 102000000412 Annexin Human genes 0.000 claims description 2
- 108050008874 Annexin Proteins 0.000 claims description 2
- 108020005544 Antisense RNA Proteins 0.000 claims description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims description 2
- 101800004538 Bradykinin Proteins 0.000 claims description 2
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 claims description 2
- 108010087806 Carnosine Proteins 0.000 claims description 2
- 108090000994 Catalytic RNA Proteins 0.000 claims description 2
- 102000053642 Catalytic RNA Human genes 0.000 claims description 2
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 claims description 2
- 206010010356 Congenital anomaly Diseases 0.000 claims description 2
- 102100023419 Cystic fibrosis transmembrane conductance regulator Human genes 0.000 claims description 2
- 102000004127 Cytokines Human genes 0.000 claims description 2
- 108090000695 Cytokines Proteins 0.000 claims description 2
- 102000000311 Cytosine Deaminase Human genes 0.000 claims description 2
- 108010080611 Cytosine Deaminase Proteins 0.000 claims description 2
- 102000001039 Dystrophin Human genes 0.000 claims description 2
- 108010069091 Dystrophin Proteins 0.000 claims description 2
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 claims description 2
- 108010067306 Fibronectins Proteins 0.000 claims description 2
- 208000015872 Gaucher disease Diseases 0.000 claims description 2
- 108010091938 HLA-B7 Antigen Proteins 0.000 claims description 2
- 101000818522 Homo sapiens fMet-Leu-Phe receptor Proteins 0.000 claims description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
- 108010031792 IGF Type 2 Receptor Proteins 0.000 claims description 2
- 206010061598 Immunodeficiency Diseases 0.000 claims description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 2
- 102000015696 Interleukins Human genes 0.000 claims description 2
- 108010063738 Interleukins Proteins 0.000 claims description 2
- 108010092694 L-Selectin Proteins 0.000 claims description 2
- 102000016551 L-selectin Human genes 0.000 claims description 2
- 102000000853 LDL receptors Human genes 0.000 claims description 2
- 108010001831 LDL receptors Proteins 0.000 claims description 2
- 108010031099 Mannose Receptor Proteins 0.000 claims description 2
- 102000019218 Mannose-6-phosphate receptors Human genes 0.000 claims description 2
- 208000021642 Muscular disease Diseases 0.000 claims description 2
- 201000009623 Myopathy Diseases 0.000 claims description 2
- BRMWTNUJHUMWMS-LURJTMIESA-N N(tele)-methyl-L-histidine Chemical compound CN1C=NC(C[C@H](N)C(O)=O)=C1 BRMWTNUJHUMWMS-LURJTMIESA-N 0.000 claims description 2
- FHQDWPCFSJMNCT-UHFFFAOYSA-N N(tele)-methylhistamine Chemical compound CN1C=NC(CCN)=C1 FHQDWPCFSJMNCT-UHFFFAOYSA-N 0.000 claims description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 2
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 claims description 2
- 229930193140 Neomycin Natural products 0.000 claims description 2
- 102000011931 Nucleoproteins Human genes 0.000 claims description 2
- 108010061100 Nucleoproteins Proteins 0.000 claims description 2
- 108010069013 Phenylalanine Hydroxylase Proteins 0.000 claims description 2
- 102100038223 Phenylalanine-4-hydroxylase Human genes 0.000 claims description 2
- 201000011252 Phenylketonuria Diseases 0.000 claims description 2
- 241000242583 Scyphozoa Species 0.000 claims description 2
- 241000700584 Simplexvirus Species 0.000 claims description 2
- 102000006601 Thymidine Kinase Human genes 0.000 claims description 2
- 108020004440 Thymidine kinase Proteins 0.000 claims description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 claims description 2
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 claims description 2
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 210000001552 airway epithelial cell Anatomy 0.000 claims description 2
- CMQZRJBJDCVIEY-JEOLMMCMSA-N alpha-L-Fucp-(1->3)-[beta-D-Galp-(1->4)]-beta-D-GlcpNAc-(1->3)-beta-D-Galp-(1->4)-D-Glcp Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)[C@@H](CO)O[C@@H](O[C@@H]2[C@H]([C@H](O[C@@H]3[C@H](OC(O)[C@H](O)[C@H]3O)CO)O[C@H](CO)[C@@H]2O)O)[C@@H]1NC(C)=O CMQZRJBJDCVIEY-JEOLMMCMSA-N 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 108010042092 antiflammin P2 Proteins 0.000 claims description 2
- 239000000427 antigen Substances 0.000 claims description 2
- 102000036639 antigens Human genes 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 claims description 2
- 229940111121 antirheumatic drug quinolines Drugs 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 230000001746 atrial effect Effects 0.000 claims description 2
- SQDFRWJUKVCUOT-KGGMAGTISA-N beta-D-Galp3S-(1->4)-[alpha-L-Fucp-(1->3)]-D-GlcpNAc Chemical class O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O)[C@@H](CO)O2)O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O SQDFRWJUKVCUOT-KGGMAGTISA-N 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims description 2
- 239000003114 blood coagulation factor Substances 0.000 claims description 2
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 229960004203 carnitine Drugs 0.000 claims description 2
- 229940044199 carnosine Drugs 0.000 claims description 2
- 210000003855 cell nucleus Anatomy 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 239000005482 chemotactic factor Substances 0.000 claims description 2
- PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 claims description 2
- 210000000805 cytoplasm Anatomy 0.000 claims description 2
- 230000007812 deficiency Effects 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 230000003511 endothelial effect Effects 0.000 claims description 2
- 102100021145 fMet-Leu-Phe receptor Human genes 0.000 claims description 2
- 210000002950 fibroblast Anatomy 0.000 claims description 2
- 229960000304 folic acid Drugs 0.000 claims description 2
- 235000019152 folic acid Nutrition 0.000 claims description 2
- 239000011724 folic acid Substances 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 2
- 210000000987 immune system Anatomy 0.000 claims description 2
- 230000007813 immunodeficiency Effects 0.000 claims description 2
- 229940047122 interleukins Drugs 0.000 claims description 2
- 230000000968 intestinal effect Effects 0.000 claims description 2
- 210000002510 keratinocyte Anatomy 0.000 claims description 2
- 210000005229 liver cell Anatomy 0.000 claims description 2
- 210000004698 lymphocyte Anatomy 0.000 claims description 2
- 230000002132 lysosomal effect Effects 0.000 claims description 2
- 210000002540 macrophage Anatomy 0.000 claims description 2
- 210000002752 melanocyte Anatomy 0.000 claims description 2
- 230000002503 metabolic effect Effects 0.000 claims description 2
- 230000001452 natriuretic effect Effects 0.000 claims description 2
- 210000000822 natural killer cell Anatomy 0.000 claims description 2
- 229960004927 neomycin Drugs 0.000 claims description 2
- 230000007514 neuronal growth Effects 0.000 claims description 2
- 229920001542 oligosaccharide Polymers 0.000 claims description 2
- 150000002482 oligosaccharides Chemical class 0.000 claims description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N ornithyl group Chemical group N[C@@H](CCCN)C(=O)O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 2
- 239000000813 peptide hormone Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 229960005179 primaquine Drugs 0.000 claims description 2
- 150000003248 quinolines Chemical class 0.000 claims description 2
- 210000003370 receptor cell Anatomy 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 108091092562 ribozyme Proteins 0.000 claims description 2
- 210000002363 skeletal muscle cell Anatomy 0.000 claims description 2
- 210000004927 skin cell Anatomy 0.000 claims description 2
- 210000002460 smooth muscle Anatomy 0.000 claims description 2
- 239000005460 tetrahydrofolate Substances 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 238000013518 transcription Methods 0.000 claims description 2
- 230000035897 transcription Effects 0.000 claims description 2
- 238000003151 transfection method Methods 0.000 claims description 2
- 239000002753 trypsin inhibitor Substances 0.000 claims description 2
- 238000002255 vaccination Methods 0.000 claims description 2
- 229940124549 vasodilator Drugs 0.000 claims description 2
- 239000003071 vasodilator agent Substances 0.000 claims description 2
- JODLANKMQFEABK-UHFFFAOYSA-N 1-(7-chloroquinolin-4-yl)-1-pentan-2-ylhydrazine Chemical compound ClC1=CC=C2C(N(N)C(C)CCC)=CC=NC2=C1 JODLANKMQFEABK-UHFFFAOYSA-N 0.000 claims 1
- CPAGZVLINCPJEH-UHFFFAOYSA-N 2-(1-methyl-1h-imidazol-5-yl)ethan-1-amine Chemical compound CN1C=NC=C1CCN CPAGZVLINCPJEH-UHFFFAOYSA-N 0.000 claims 1
- 102100037362 Fibronectin Human genes 0.000 claims 1
- 241000371980 Influenza B virus (B/Shanghai/361/2002) Species 0.000 claims 1
- 102100035792 Kininogen-1 Human genes 0.000 claims 1
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 239000003184 complementary RNA Substances 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 claims 1
- WHNFPRLDDSXQCL-UAZQEYIDSA-N α-msh Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H](CO)NC(C)=O)C1=CC=C(O)C=C1 WHNFPRLDDSXQCL-UAZQEYIDSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 52
- 238000000034 method Methods 0.000 description 40
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 34
- 108010015899 Glycopeptides Proteins 0.000 description 30
- 102000002068 Glycopeptides Human genes 0.000 description 30
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 29
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 22
- -1 cetylacetyl Chemical group 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical class S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 18
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 17
- 229960003677 chloroquine Drugs 0.000 description 17
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 17
- 239000003960 organic solvent Substances 0.000 description 17
- 238000005119 centrifugation Methods 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 14
- 239000012091 fetal bovine serum Substances 0.000 description 14
- 150000003839 salts Chemical class 0.000 description 13
- 238000005859 coupling reaction Methods 0.000 description 11
- 239000008188 pellet Substances 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 239000002502 liposome Substances 0.000 description 10
- 238000002156 mixing Methods 0.000 description 10
- 230000008878 coupling Effects 0.000 description 9
- 238000010168 coupling process Methods 0.000 description 9
- 229960003681 gluconolactone Drugs 0.000 description 9
- 238000011534 incubation Methods 0.000 description 9
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 8
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 8
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 7
- 125000005414 dithiopyridyl group Chemical group 0.000 description 7
- 230000002185 fusiogenic effect Effects 0.000 description 7
- 230000004927 fusion Effects 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 150000007524 organic acids Chemical class 0.000 description 7
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000004020 luminiscence type Methods 0.000 description 6
- 229920002704 polyhistidine Polymers 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 241000701161 unidentified adenovirus Species 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000007822 coupling agent Substances 0.000 description 5
- 230000000368 destabilizing effect Effects 0.000 description 5
- HNXQXTQTPAJEJL-UHFFFAOYSA-N 2-aminopteridin-4-ol Chemical compound C1=CN=C2NC(N)=NC(=O)C2=N1 HNXQXTQTPAJEJL-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 229920002307 Dextran Polymers 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 125000002091 cationic group Chemical group 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- CYWHLOXWVAWMFO-UHFFFAOYSA-N 3-sulfanyl-1h-pyridine-2-thione Chemical compound SC1=CC=CN=C1S CYWHLOXWVAWMFO-UHFFFAOYSA-N 0.000 description 3
- 101150096822 Fuca1 gene Proteins 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical group Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000005349 anion exchange Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 3
- 210000003712 lysosome Anatomy 0.000 description 3
- 230000001868 lysosomic effect Effects 0.000 description 3
- 230000034217 membrane fusion Effects 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000012064 sodium phosphate buffer Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- GKSPIZSKQWTXQG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[1-(pyridin-2-yldisulfanyl)ethyl]benzoate Chemical compound C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SSC1=CC=CC=N1 GKSPIZSKQWTXQG-UHFFFAOYSA-N 0.000 description 2
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 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
- 241001529936 Murinae Species 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000004833 X-ray photoelectron spectroscopy Methods 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 2
- 229920000447 polyanionic polymer Polymers 0.000 description 2
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- NKUZQMZWTZAPSN-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-bromoacetate Chemical compound BrCC(=O)ON1C(=O)CCC1=O NKUZQMZWTZAPSN-UHFFFAOYSA-N 0.000 description 1
- UVGHPGOONBRLCX-NJSLBKSFSA-N (2,5-dioxopyrrolidin-1-yl) 6-[5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoate Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)NCCCCCC(=O)ON1C(=O)CCC1=O UVGHPGOONBRLCX-NJSLBKSFSA-N 0.000 description 1
- FUKOTTQGWQVMQB-UHFFFAOYSA-N (2-bromoacetyl) 2-bromoacetate Chemical compound BrCC(=O)OC(=O)CBr FUKOTTQGWQVMQB-UHFFFAOYSA-N 0.000 description 1
- CKFPFHVZNFYBHC-FSPLSTOPSA-N (2s)-2-amino-3-[3-[(2s)-2-aminopropanoyl]imidazol-4-yl]propanoic acid Chemical compound C[C@H](N)C(=O)N1C=NC=C1C[C@H](N)C(O)=O CKFPFHVZNFYBHC-FSPLSTOPSA-N 0.000 description 1
- PQMRRAQXKWFYQN-UHFFFAOYSA-N 1-phenyl-2-sulfanylideneimidazolidin-4-one Chemical compound S=C1NC(=O)CN1C1=CC=CC=C1 PQMRRAQXKWFYQN-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical class NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
- QRVGGFTWNNKAQA-UHFFFAOYSA-N 4-N-(6-methoxyquinolin-2-yl)pentane-1,4-diamine Chemical compound NCCCC(C)NC1=NC2=CC=C(C=C2C=C1)OC QRVGGFTWNNKAQA-UHFFFAOYSA-N 0.000 description 1
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- OKTJSMMVPCPJKN-IGMARMGPSA-N Carbon-12 Chemical group [12C] OKTJSMMVPCPJKN-IGMARMGPSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- QTANTQQOYSUMLC-UHFFFAOYSA-O Ethidium cation Chemical compound C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 QTANTQQOYSUMLC-UHFFFAOYSA-O 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 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
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- 101800000597 N-terminal peptide Proteins 0.000 description 1
- 102400000108 N-terminal peptide Human genes 0.000 description 1
- 229910017974 NH40H Inorganic materials 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 108010059722 Viral Fusion Proteins Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 108010084541 asialoorosomucoid Proteins 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- KDPAWGWELVVRCH-UHFFFAOYSA-N bromoacetic acid Chemical class OC(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- OKTJSMMVPCPJKN-BJUDXGSMSA-N carbon-11 Chemical group [11C] OKTJSMMVPCPJKN-BJUDXGSMSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 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 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 230000001295 genetical effect Effects 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229960003971 influenza vaccine Drugs 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000008371 intracellularly ATP-gated chloride channel activity proteins Human genes 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- UEICEJLUNGARHQ-UHFFFAOYSA-N pentane-1,4-diamine Chemical compound CC(N)CCCN UEICEJLUNGARHQ-UHFFFAOYSA-N 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 108010055896 polyornithine Proteins 0.000 description 1
- 229920002714 polyornithine Polymers 0.000 description 1
- 238000002165 resonance energy transfer Methods 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
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Virology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9613990A FR2755976B1 (fr) | 1996-11-15 | 1996-11-15 | Nouveaux complexes d'acides nucleiques et de polymere substitue par des residus entrainant la destabilisation des membranes cellulaires |
| FR96/13990 | 1996-11-15 | ||
| PCT/FR1997/002022 WO1998022610A1 (fr) | 1996-11-15 | 1997-11-10 | Nouveaux complexes polymeriques pour la transfection d'acides nucleiques, avec des residus destabilisant des membranes cellulaires |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2267833A1 true CA2267833A1 (fr) | 1998-05-28 |
Family
ID=9497684
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002267833A Abandoned CA2267833A1 (fr) | 1996-11-15 | 1997-11-10 | Nouveaux complexes polymeriques pour la transfection d'acides nucleiques, avec des residus destabilisant des membranes cellulaires |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6372499B1 (enExample) |
| EP (1) | EP0946744B1 (enExample) |
| JP (1) | JP2001504344A (enExample) |
| AT (1) | ATE274066T1 (enExample) |
| AU (1) | AU742818B2 (enExample) |
| CA (1) | CA2267833A1 (enExample) |
| DE (1) | DE69730348T2 (enExample) |
| ES (1) | ES2225992T3 (enExample) |
| FR (1) | FR2755976B1 (enExample) |
| IL (1) | IL128912A (enExample) |
| WO (1) | WO1998022610A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6919076B1 (en) | 1998-01-20 | 2005-07-19 | Pericor Science, Inc. | Conjugates of agents and transglutaminase substrate linking molecules |
| CA2348823A1 (en) * | 1998-12-02 | 2000-06-08 | I.D.M. Immuno-Designed Molecules | New oligomeric conjugates liable to transfer biological molecules into cells |
| AU7352200A (en) * | 1999-09-01 | 2001-03-26 | Regents Of The University Of California, The | Novel natriuretic peptide receptors, interacting compounds and methods of regulating proliferation and/or survival of neurons |
| US7070807B2 (en) | 1999-12-29 | 2006-07-04 | Mixson A James | Branched histidine copolymers and methods for using same |
| EP1242052A4 (en) * | 1999-12-29 | 2003-07-02 | A James Mixson | HISTIDIN COPOLYMER AND METHODS OF USE THEREOF |
| CA2797652C (en) * | 2000-07-21 | 2016-03-08 | Revance Therapeutics, Inc. | Multi-component biological transport systems |
| FR2812658B1 (fr) * | 2000-08-01 | 2005-04-15 | De Bruno Vandiere | Procede d'analyse d'acides nucleiques |
| US7465708B2 (en) | 2002-11-25 | 2008-12-16 | Mixson A James | Branched cationic copolymers and methods for antimicrobial use |
| AU2005251676B2 (en) | 2004-03-03 | 2011-09-29 | Revance Therapeutics, Inc. | Compositions and methods for topical diagnostic and therapeutic transport |
| US9211248B2 (en) | 2004-03-03 | 2015-12-15 | Revance Therapeutics, Inc. | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
| US7740861B2 (en) * | 2004-06-16 | 2010-06-22 | University Of Massachusetts | Drug delivery product and methods |
| US20060040879A1 (en) * | 2004-08-21 | 2006-02-23 | Kosak Kenneth M | Chloroquine coupled nucleic acids and methods for their synthesis |
| CN101052383B (zh) | 2004-09-17 | 2013-01-30 | 马萨诸塞大学 | 用于溶酶体酶缺乏症的组合物和其用途 |
| US20060094104A1 (en) * | 2004-10-29 | 2006-05-04 | Leopold Grillberger | Animal protein-free media for cultivation of cells |
| US20060211004A1 (en) | 2005-02-15 | 2006-09-21 | Ilsley Diane D | Methods and compositions for determining non-specific cytotoxicity of a transfection agent |
| BRPI0608249A2 (pt) | 2005-03-03 | 2009-12-08 | Revance Therapeutics Inc | formulação, método para aplicação tópica e kit para distribuição transdérmica de toxina botulìnica |
| WO2007050643A2 (en) * | 2005-10-24 | 2007-05-03 | University Of Massachusetts | Compositions and their uses for gene therapy of bone conditions |
| JP2011517279A (ja) * | 2007-10-29 | 2011-06-02 | ユニバーシティ オブ マサチューセッツ | 核酸(siRNA)送達用の酵母細胞壁粒子(YCWP)多層状ナノ粒子 |
| FR2928373B1 (fr) * | 2008-03-05 | 2010-12-31 | Centre Nat Rech Scient | Polymere derive de la polyethylenimine lineaire pour le transfert de gene. |
| WO2010008582A2 (en) | 2008-07-18 | 2010-01-21 | Rxi Pharmaceuticals Corporation | Phagocytic cell drug delivery system |
| CN108165548B (zh) | 2008-09-22 | 2022-10-14 | 菲奥医药公司 | 减小大小的自递送RNAi化合物 |
| WO2010078536A1 (en) | 2009-01-05 | 2010-07-08 | Rxi Pharmaceuticals Corporation | Inhibition of pcsk9 through rnai |
| WO2012115772A2 (en) | 2011-02-25 | 2012-08-30 | Medtronic, Inc. | Therapy for kidney disease and/or heart failure |
| EP2750697A4 (en) | 2011-09-02 | 2015-03-25 | Medtronic Inc | CHIMERIC NATRIURETIC PEPTIDE COMPOSITIONS AND METHOD FOR THE PRODUCTION THEREOF |
| US9162191B2 (en) * | 2012-11-15 | 2015-10-20 | Board Of Trustees Of The University Of Alabama | Imidazole-containing polymer membranes and methods of use |
| CN102949729B (zh) * | 2012-11-20 | 2014-06-18 | 中国科学院宁波材料技术与工程研究所 | 主动靶向型小干扰核糖核酸输送载体及其制备方法 |
| AR122446A1 (es) * | 2020-04-29 | 2022-09-14 | Medimmune Llc | Composiciones y métodos para suministrar agentes farmacéuticamente activos |
| WO2022189361A1 (en) * | 2021-03-08 | 2022-09-15 | Universiteit Gent | Conjugates including multiple saccharidic chains on a linear protein and uses in mammals feed |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1316990A (en) * | 1970-09-17 | 1973-05-16 | Roche Products Ltd | Imidazolyl derivatives |
| US5166320A (en) * | 1987-04-22 | 1992-11-24 | University Of Connecticut | Carrier system and method for the introduction of genes into mammalian cells |
| JP2827287B2 (ja) * | 1988-07-05 | 1998-11-25 | 武田薬品工業株式会社 | 水溶性薬物含有徐放型マイクロカプセル |
| US5354844A (en) * | 1989-03-16 | 1994-10-11 | Boehringer Ingelheim International Gmbh | Protein-polycation conjugates |
| ES2090049T3 (es) * | 1989-03-16 | 1996-10-16 | Boehringer Ingelheim Int | Unidades geneticas para la inhibicion de la funcion de arn. |
| WO1992011037A2 (en) * | 1990-12-19 | 1992-07-09 | Advanced Magnetics Inc. | Targeting of therapeutic agents using polysaccharides |
| DE4104186A1 (de) * | 1991-02-12 | 1992-08-13 | Genentech Inc | Neue, ueber endozytose in hoehere eukaryotische zellen aufnehmbare, nukleinsaeure enthaltende komplexe |
| WO1993009176A2 (en) * | 1991-10-29 | 1993-05-13 | Clover Consolidated, Limited | Crosslinkable polysaccharides, polycations and lipids useful for encapsulation and drug release |
| DK0636028T3 (da) * | 1992-04-03 | 2004-07-12 | Univ California | Selvorganiserende polynucleotidleveringssystem omfattende et amfipatisk kationisk peptid |
| FR2719316B1 (fr) * | 1994-04-28 | 1996-05-31 | Idm | Nouveaux complexes d'acide nucléique et de polymère, leur procédé de préparation et leur utilisation pour la transfection de cellules. |
| US5733762A (en) * | 1994-04-28 | 1998-03-31 | I.D.M. Immuno-Designed Molecules | Complexes of nucleic acid and polymer, their process of preparation and their use for the transfection of cells |
| US6030941A (en) * | 1996-05-01 | 2000-02-29 | Avi Biopharma, Inc. | Polymer composition for delivering substances in living organisms |
-
1996
- 1996-11-15 FR FR9613990A patent/FR2755976B1/fr not_active Expired - Fee Related
-
1997
- 1997-11-10 WO PCT/FR1997/002022 patent/WO1998022610A1/fr not_active Ceased
- 1997-11-10 AT AT97945903T patent/ATE274066T1/de not_active IP Right Cessation
- 1997-11-10 IL IL128912A patent/IL128912A/en not_active IP Right Cessation
- 1997-11-10 US US09/297,519 patent/US6372499B1/en not_active Expired - Fee Related
- 1997-11-10 JP JP52325798A patent/JP2001504344A/ja not_active Ceased
- 1997-11-10 EP EP97945903A patent/EP0946744B1/fr not_active Expired - Lifetime
- 1997-11-10 CA CA002267833A patent/CA2267833A1/fr not_active Abandoned
- 1997-11-10 AU AU51239/98A patent/AU742818B2/en not_active Ceased
- 1997-11-10 ES ES97945903T patent/ES2225992T3/es not_active Expired - Lifetime
- 1997-11-10 DE DE69730348T patent/DE69730348T2/de not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES2225992T3 (es) | 2005-03-16 |
| ATE274066T1 (de) | 2004-09-15 |
| FR2755976B1 (fr) | 1999-01-15 |
| EP0946744A1 (fr) | 1999-10-06 |
| AU742818B2 (en) | 2002-01-10 |
| EP0946744B1 (fr) | 2004-08-18 |
| DE69730348T2 (de) | 2005-09-01 |
| DE69730348D1 (de) | 2004-09-23 |
| FR2755976A1 (fr) | 1998-05-22 |
| US6372499B1 (en) | 2002-04-16 |
| JP2001504344A (ja) | 2001-04-03 |
| WO1998022610A1 (fr) | 1998-05-28 |
| IL128912A0 (en) | 2000-02-17 |
| IL128912A (en) | 2006-06-11 |
| AU5123998A (en) | 1998-06-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0946744B1 (fr) | Nouveaux complexes polymeriques pour la transfection d'acides nucleiques, avec des residus destabilisant des membranes cellulaires | |
| EP0753070B1 (fr) | Nouveaux complexes d'acide nucleique et de polymere, leur procede de preparation et leur utilisation pour la transfection de cellules | |
| Midoux et al. | Chemical vectors for gene delivery: a current review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers | |
| Gao et al. | Targeting delivery of oligonucleotide and plasmid DNA to hepatocyte via galactosylated chitosan vector | |
| AU681735B2 (en) | Self-assembling polynucleotide delivery system comprising dendrimer polycations | |
| Midoux et al. | Polymer-based gene delivery: a current review on the uptake and intracellular trafficking of polyplexes | |
| US7737108B1 (en) | Enhanced transport using membrane disruptive agents | |
| US20060159764A1 (en) | Process of making a compound by forming a polymer from a template drug | |
| Boeckle et al. | C‐versus N‐terminally linked melittin‐polyethylenimine conjugates: the site of linkage strongly influences activity of DNA polyplexes | |
| US5990089A (en) | Self-assembling polynucleotide delivery system comprising dendrimer polycations | |
| Berger et al. | Optimizing pDNA lipo-polyplexes: a balancing act between stability and cargo release | |
| HUE026811T2 (en) | Compositions for targeted delivery of sirna | |
| WO2001007486A1 (en) | A biodegradable polycation composition for delivery of an anionic macromolecule | |
| JPH11506722A (ja) | 細胞に核酸を送達するための核酸運搬体 | |
| FR2928373A1 (fr) | Polymere derive de la polyethylenimine lineaire pour le transfert de gene. | |
| Nouri et al. | Reducing the Visibility of the Vector/DNA Nanocomplexes to the Immune System by Elastin-Like Peptides. | |
| Larsen et al. | Using the epigenetic code to promote the unpackaging and transcriptional activation of DNA polyplexes for gene delivery | |
| Wang et al. | Engineered lipid nanoparticles with synergistic dendritic cell targeting and enhanced endosomal escape for boosted mRNA cancer vaccines | |
| Anwer et al. | Synthetic glycopeptide-based delivery systems for systemic gene targeting to hepatocytes | |
| JP7068711B2 (ja) | 細胞質送達ペプチド | |
| Heidel et al. | Molecular conjugates | |
| White | Novel Bioconjugate Strategies to Improve Nonviral Gene Deliver to Liver: Systematic Optimization of Multi-Component Delivery Vehicles | |
| Fernandez | Development of PEGylated polyacridine peptides for in vivo gene delivery of plasmid DNA | |
| Klöckner | Novel biodegradable gene carriers based on oligomerized polyamines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |