CA3049197C - A drug delivery system comprising virus-like particles from john cunningham virus and methods providing thereof - Google Patents
A drug delivery system comprising virus-like particles from john cunningham virus and methods providing thereof Download PDFInfo
- Publication number
- CA3049197C CA3049197C CA3049197A CA3049197A CA3049197C CA 3049197 C CA3049197 C CA 3049197C CA 3049197 A CA3049197 A CA 3049197A CA 3049197 A CA3049197 A CA 3049197A CA 3049197 C CA3049197 C CA 3049197C
- Authority
- CA
- Canada
- Prior art keywords
- vlp
- composition
- pentamers
- drug delivery
- delivery system
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 113
- 238000012377 drug delivery Methods 0.000 title claims abstract description 81
- 239000002245 particle Substances 0.000 title claims abstract description 35
- 241000700605 Viruses Species 0.000 title claims abstract description 20
- 230000008499 blood brain barrier function Effects 0.000 claims abstract description 86
- 210000001218 blood-brain barrier Anatomy 0.000 claims abstract description 86
- 239000000203 mixture Substances 0.000 claims description 135
- 101710132601 Capsid protein Proteins 0.000 claims description 73
- 101710197658 Capsid protein VP1 Proteins 0.000 claims description 73
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 claims description 73
- 101710108545 Viral protein 1 Proteins 0.000 claims description 73
- 230000001939 inductive effect Effects 0.000 claims description 40
- 230000002776 aggregation Effects 0.000 claims description 38
- 238000004220 aggregation Methods 0.000 claims description 38
- 210000000234 capsid Anatomy 0.000 claims description 32
- 238000001556 precipitation Methods 0.000 claims description 26
- 239000003795 chemical substances by application Substances 0.000 claims description 25
- 210000003169 central nervous system Anatomy 0.000 claims description 24
- 238000000502 dialysis Methods 0.000 claims description 24
- 230000001965 increasing effect Effects 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 22
- 150000007523 nucleic acids Chemical class 0.000 claims description 21
- 108020004707 nucleic acids Proteins 0.000 claims description 20
- 102000039446 nucleic acids Human genes 0.000 claims description 20
- 150000001413 amino acids Chemical group 0.000 claims description 19
- 230000035699 permeability Effects 0.000 claims description 18
- 239000000872 buffer Substances 0.000 claims description 17
- 235000001014 amino acid Nutrition 0.000 claims description 15
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 15
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 15
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 15
- 239000002773 nucleotide Substances 0.000 claims description 14
- 125000003729 nucleotide group Chemical group 0.000 claims description 14
- 208000012902 Nervous system disease Diseases 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 12
- 150000001450 anions Chemical class 0.000 claims description 12
- 239000001110 calcium chloride Substances 0.000 claims description 12
- 235000011148 calcium chloride Nutrition 0.000 claims description 12
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 9
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 229920005862 polyol Polymers 0.000 claims description 7
- 150000003077 polyols Chemical class 0.000 claims description 7
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 6
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims description 5
- 150000001768 cations Chemical class 0.000 claims description 5
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 5
- 238000000746 purification Methods 0.000 claims description 5
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 239000000824 cytostatic agent Substances 0.000 claims description 4
- 230000001085 cytostatic effect Effects 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- 150000003384 small molecules Chemical class 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Inorganic materials [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 claims description 3
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 claims description 3
- 229910052792 caesium Inorganic materials 0.000 claims description 3
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 229910052701 rubidium Inorganic materials 0.000 claims description 3
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 claims description 3
- NCCSSGKUIKYAJD-UHFFFAOYSA-N rubidium(1+) Chemical compound [Rb+] NCCSSGKUIKYAJD-UHFFFAOYSA-N 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 3
- 235000011152 sodium sulphate Nutrition 0.000 claims description 3
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000004471 Glycine Substances 0.000 claims description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 2
- 239000007832 Na2SO4 Substances 0.000 claims description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 235000004279 alanine Nutrition 0.000 claims description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 235000000346 sugar Nutrition 0.000 claims description 2
- MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical compound C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 claims 1
- 229910000388 diammonium phosphate Inorganic materials 0.000 claims 1
- 235000019838 diammonium phosphate Nutrition 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 41
- 108090000623 proteins and genes Proteins 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 30
- 235000018102 proteins Nutrition 0.000 description 27
- 238000002296 dynamic light scattering Methods 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
- 239000000825 pharmaceutical preparation Substances 0.000 description 20
- 229940127557 pharmaceutical product Drugs 0.000 description 20
- 239000013612 plasmid Substances 0.000 description 20
- 238000003860 storage Methods 0.000 description 19
- 108060001084 Luciferase Proteins 0.000 description 16
- 239000005089 Luciferase Substances 0.000 description 16
- 125000003275 alpha amino acid group Chemical group 0.000 description 16
- 239000000463 material Substances 0.000 description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
- 238000009826 distribution Methods 0.000 description 15
- 238000007710 freezing Methods 0.000 description 15
- 230000008014 freezing Effects 0.000 description 15
- 210000004556 brain Anatomy 0.000 description 14
- 230000014509 gene expression Effects 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 230000005526 G1 to G0 transition Effects 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000006698 induction Effects 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 101710172711 Structural protein Proteins 0.000 description 8
- 108010087302 Viral Structural Proteins Proteins 0.000 description 8
- 208000015114 central nervous system disease Diseases 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- -1 thrombolytics Substances 0.000 description 8
- 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 7
- 238000012432 intermediate storage Methods 0.000 description 7
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 7
- 238000004806 packaging method and process Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 238000005571 anion exchange chromatography Methods 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 238000000569 multi-angle light scattering Methods 0.000 description 6
- 238000001542 size-exclusion chromatography Methods 0.000 description 6
- 101710163270 Nuclease Proteins 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 5
- 238000003501 co-culture Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000004962 physiological condition Effects 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 208000034628 Celiac artery compression syndrome Diseases 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 208000025966 Neurological disease Diseases 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000004888 barrier function Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000002490 cerebral effect Effects 0.000 description 4
- 239000002738 chelating agent Substances 0.000 description 4
- 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 4
- 208000035475 disorder Diseases 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000009343 monoculture Methods 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 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 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 108700043045 nanoluc Proteins 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000004627 transmission electron microscopy Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 238000002604 ultrasonography Methods 0.000 description 3
- 241000701447 unidentified baculovirus Species 0.000 description 3
- 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 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
- 208000005793 Restless legs syndrome Diseases 0.000 description 2
- 108010034546 Serratia marcescens nuclease Proteins 0.000 description 2
- 241000256251 Spodoptera frugiperda Species 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 208000032109 Transient ischaemic attack Diseases 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 206010047141 Vasodilatation Diseases 0.000 description 2
- 108010067390 Viral Proteins Proteins 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 150000003862 amino acid derivatives Chemical class 0.000 description 2
- 239000000611 antibody drug conjugate Substances 0.000 description 2
- 229940049595 antibody-drug conjugate Drugs 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 229960003237 betaine Drugs 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000005277 cation exchange chromatography Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 201000003631 narcolepsy Diseases 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 2
- 229910052939 potassium sulfate Inorganic materials 0.000 description 2
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000011146 sterile filtration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 201000010875 transient cerebral ischemia Diseases 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 238000009827 uniform distribution Methods 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KIIBBJKLKFTNQO-WHFBIAKZSA-N 5-hydroxyectoine Chemical compound CC1=N[C@H](C(O)=O)[C@@H](O)CN1 KIIBBJKLKFTNQO-WHFBIAKZSA-N 0.000 description 1
- 206010054196 Affect lability Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 102000014461 Ataxins Human genes 0.000 description 1
- 108010078286 Ataxins Proteins 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 208000033001 Complex partial seizures Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 206010013642 Drooling Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000034846 Familial Amyloid Neuropathies Diseases 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 208000001914 Fragile X syndrome Diseases 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- 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 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 206010019889 Hereditary neuropathic amyloidosis Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 206010020853 Hypertonic bladder Diseases 0.000 description 1
- 241000701460 JC polyomavirus Species 0.000 description 1
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 206010028391 Musculoskeletal Pain Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
- 206010057852 Nicotine dependence Diseases 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 208000030053 Opioid-Induced Constipation Diseases 0.000 description 1
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 108010071690 Prealbumin Proteins 0.000 description 1
- 208000027030 Premenstrual dysphoric disease Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 208000018642 Semantic dementia Diseases 0.000 description 1
- 208000008630 Sialorrhea Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 208000025569 Tobacco Use disease Diseases 0.000 description 1
- 206010044074 Torticollis Diseases 0.000 description 1
- 102000009190 Transthyretin Human genes 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000002205 anti-dementic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 1
- 208000018300 basal ganglia disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 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 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 201000002866 cervical dystonia Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940096422 collagen type i Drugs 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000009295 crossflow filtration Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- WQXNXVUDBPYKBA-YFKPBYRVSA-N ectoine Chemical compound CC1=[NH+][C@H](C([O-])=O)CCN1 WQXNXVUDBPYKBA-YFKPBYRVSA-N 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 238000001825 field-flow fractionation Methods 0.000 description 1
- 238000001249 flow field-flow fractionation Methods 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 239000003825 glutamate receptor antagonist Substances 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 210000005063 microvascular endothelium Anatomy 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 208000027061 mild cognitive impairment Diseases 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 208000017376 neurovascular disease Diseases 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 210000000869 occipital lobe Anatomy 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 208000020629 overactive bladder Diseases 0.000 description 1
- 210000001152 parietal lobe Anatomy 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 239000003368 psychostimulant agent Substances 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000000518 rheometry Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 230000005586 smoking cessation Effects 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002849 thermal shift Methods 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 201000007905 transthyretin amyloidosis Diseases 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5176—Compounds of unknown constitution, e.g. material from plants or animals
- A61K9/5184—Virus capsids or envelopes enclosing drugs
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/06—Sulfuric ester hydrolases (3.1.6)
- C12Y301/06001—Arylsulfatase (3.1.6.1)
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/22011—Polyomaviridae, e.g. polyoma, SV40, JC
- C12N2710/22022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/22011—Polyomaviridae, e.g. polyoma, SV40, JC
- C12N2710/22023—Virus like particles [VLP]
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/22011—Polyomaviridae, e.g. polyoma, SV40, JC
- C12N2710/22032—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/22011—Polyomaviridae, e.g. polyoma, SV40, JC
- C12N2710/22041—Use of virus, viral particle or viral elements as a vector
- C12N2710/22042—Use of virus, viral particle or viral elements as a vector virus or viral particle as vehicle, e.g. encapsulating small organic molecule
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/22011—Polyomaviridae, e.g. polyoma, SV40, JC
- C12N2710/22051—Methods of production or purification of viral material
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Botany (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Optics & Photonics (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Nanotechnology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2018/085699 WO2020125962A1 (en) | 2018-12-18 | 2018-12-18 | A novel drug delivery system and methods providing thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA3049197A1 CA3049197A1 (en) | 2020-05-18 |
| CA3049197C true CA3049197C (en) | 2023-01-03 |
Family
ID=65009711
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3049197A Active CA3049197C (en) | 2018-12-18 | 2018-12-18 | A drug delivery system comprising virus-like particles from john cunningham virus and methods providing thereof |
| CA3121689A Pending CA3121689A1 (en) | 2018-12-18 | 2019-10-14 | A method for providing a vlp derived from john cunningham virus |
| CA3065548A Pending CA3065548A1 (en) | 2018-12-18 | 2019-12-16 | Vlp for the treatment of a lysosomal storage disease |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3121689A Pending CA3121689A1 (en) | 2018-12-18 | 2019-10-14 | A method for providing a vlp derived from john cunningham virus |
| CA3065548A Pending CA3065548A1 (en) | 2018-12-18 | 2019-12-16 | Vlp for the treatment of a lysosomal storage disease |
Country Status (12)
| Country | Link |
|---|---|
| US (4) | US11279938B2 (enExample) |
| EP (2) | EP3688147B8 (enExample) |
| JP (3) | JP6884432B2 (enExample) |
| CN (3) | CN111587289B (enExample) |
| BR (3) | BR112019014209A2 (enExample) |
| CA (3) | CA3049197C (enExample) |
| DK (1) | DK3688147T3 (enExample) |
| ES (1) | ES2933275T3 (enExample) |
| HU (1) | HUE060952T2 (enExample) |
| PL (1) | PL3688147T3 (enExample) |
| SI (1) | SI3688147T1 (enExample) |
| WO (4) | WO2020125962A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115968403A (zh) * | 2020-05-22 | 2023-04-14 | 纽卫制药有限公司 | 用于治疗脑白质营养不良的vlp |
| WO2022227287A1 (zh) * | 2021-04-25 | 2022-11-03 | 中南大学 | Dnj及其衍生物在制备预防和/或治疗肺动脉高压药物中的应用 |
| CN115448980A (zh) * | 2021-06-08 | 2022-12-09 | 戴德森医疗财团法人嘉义基督教医院 | 表面链结标靶多肽的类病毒颗粒及其用途 |
| EP4166672A1 (en) | 2021-10-15 | 2023-04-19 | NEUWAY Pharma GmbH | A novel method for purification of protein- or peptide-based capsules |
| WO2024079361A1 (en) | 2022-10-14 | 2024-04-18 | Neuway Pharma Gmbh | A PROTEIN- OR PEPTIDE-BASED CAPSULE (PPC), PREFERABLY A VLP, LOADED WITH A MESSENGER RNA (mRNA) AND A METHOD OF PRODUCTION AND PURIFICATION THEREOF |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19543553B4 (de) | 1995-11-22 | 2009-04-09 | Deutsches Primatenzentrum Gmbh | VP-Antigene des JC-Virus |
| EP1463512B1 (en) | 2002-01-11 | 2014-05-28 | biOasis Technologies Inc. | Use of p97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes |
| US7442372B2 (en) | 2003-08-29 | 2008-10-28 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| FR2920158B1 (fr) | 2007-08-24 | 2010-03-12 | Centre Nat Rech Scient | Production de plasmides et expression de proteines recombinantes dans des cellules cultivees sans antibiotiques |
| EP2554664A1 (de) | 2011-08-02 | 2013-02-06 | Life Science Inkubator | Verfahren zur Aufreinigung von Virus-ähnlichen Partikeln (VLP) |
| EP2636746A1 (en) | 2012-03-06 | 2013-09-11 | Life Science Inkubator | A novel drug delivery system based on JCV-VLP |
| JP6634073B2 (ja) * | 2014-05-14 | 2020-01-22 | エステベ ファーマシューティカルズ, ソシエダッド アノニマEsteve Pharmaceuticals, S.A. | リソソーム蓄積症処置用のアデノ随伴ウイルスベクター |
-
2018
- 2018-12-18 EP EP18830794.6A patent/EP3688147B8/en active Active
- 2018-12-18 CA CA3049197A patent/CA3049197C/en active Active
- 2018-12-18 BR BR112019014209-6A patent/BR112019014209A2/pt not_active Application Discontinuation
- 2018-12-18 WO PCT/EP2018/085699 patent/WO2020125962A1/en not_active Ceased
- 2018-12-18 CN CN201880006448.0A patent/CN111587289B/zh not_active Expired - Fee Related
- 2018-12-18 SI SI201830824T patent/SI3688147T1/sl unknown
- 2018-12-18 DK DK18830794.6T patent/DK3688147T3/da active
- 2018-12-18 ES ES18830794T patent/ES2933275T3/es active Active
- 2018-12-18 PL PL18830794.6T patent/PL3688147T3/pl unknown
- 2018-12-18 US US16/476,724 patent/US11279938B2/en active Active
- 2018-12-18 HU HUE18830794A patent/HUE060952T2/hu unknown
- 2018-12-18 JP JP2019538254A patent/JP6884432B2/ja not_active Expired - Fee Related
-
2019
- 2019-04-26 WO PCT/EP2019/060814 patent/WO2020126116A1/en not_active Ceased
- 2019-10-14 WO PCT/EP2019/077807 patent/WO2020126151A1/en not_active Ceased
- 2019-10-14 US US17/311,480 patent/US20230157972A1/en not_active Abandoned
- 2019-10-14 BR BR112021010758-4A patent/BR112021010758A2/pt unknown
- 2019-10-14 CA CA3121689A patent/CA3121689A1/en active Pending
- 2019-12-16 BR BR102019026837-9A patent/BR102019026837A2/pt not_active IP Right Cessation
- 2019-12-16 CA CA3065548A patent/CA3065548A1/en active Pending
- 2019-12-17 JP JP2019227342A patent/JP2020105169A/ja active Pending
- 2019-12-17 US US16/717,033 patent/US20200224205A1/en not_active Abandoned
- 2019-12-17 CN CN201911300544.9A patent/CN111333702A/zh active Pending
-
2020
- 2020-10-13 EP EP20789150.8A patent/EP4045638A1/en not_active Withdrawn
- 2020-10-13 JP JP2022521659A patent/JP2022551531A/ja active Pending
- 2020-10-13 WO PCT/EP2020/078733 patent/WO2021074123A1/en not_active Ceased
- 2020-10-13 CN CN202080081855.5A patent/CN115135757A/zh active Pending
-
2022
- 2022-11-07 US US18/053,198 patent/US20230159938A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2022551531A (ja) | 2022-12-09 |
| US11279938B2 (en) | 2022-03-22 |
| CN111333702A (zh) | 2020-06-26 |
| CN111587289A (zh) | 2020-08-25 |
| HUE060952T2 (hu) | 2023-05-28 |
| US20230157972A1 (en) | 2023-05-25 |
| EP3688147B8 (en) | 2022-10-26 |
| JP2020105169A (ja) | 2020-07-09 |
| DK3688147T3 (da) | 2022-12-19 |
| US20210301302A1 (en) | 2021-09-30 |
| CA3121689A1 (en) | 2020-06-25 |
| PL3688147T3 (pl) | 2023-01-09 |
| CA3065548A1 (en) | 2020-06-18 |
| EP4045638A1 (en) | 2022-08-24 |
| ES2933275T3 (es) | 2023-02-03 |
| SI3688147T1 (sl) | 2023-03-31 |
| CN111587289B (zh) | 2024-04-12 |
| CN115135757A (zh) | 2022-09-30 |
| WO2020125962A1 (en) | 2020-06-25 |
| US20230159938A1 (en) | 2023-05-25 |
| US20200224205A1 (en) | 2020-07-16 |
| WO2021074123A1 (en) | 2021-04-22 |
| EP3688147B1 (en) | 2022-09-14 |
| BR112019014209A2 (pt) | 2021-09-28 |
| WO2020126151A1 (en) | 2020-06-25 |
| BR112021010758A2 (pt) | 2021-08-31 |
| JP6884432B2 (ja) | 2021-06-09 |
| CA3049197A1 (en) | 2020-05-18 |
| BR102019026837A2 (pt) | 2020-10-27 |
| WO2020126116A1 (en) | 2020-06-25 |
| EP3688147A1 (en) | 2020-08-05 |
| JP2021502951A (ja) | 2021-02-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA3049197C (en) | A drug delivery system comprising virus-like particles from john cunningham virus and methods providing thereof | |
| JP2024164003A (ja) | ナノ粒子に自己組織化するポリペプチド | |
| Zhang et al. | A smart DNA hydrogel for isolation of bacterial outer membrane vesicles and localized cancer immunotherapy | |
| HK40035156B (en) | A novel drug delivery system and methods providing thereof | |
| HK40035156A (en) | A novel drug delivery system and methods providing thereof | |
| US20230310652A1 (en) | Vlp for the treatment of leukodystrophies | |
| EP3670652A1 (en) | Vlp for the treatment of a lysosomal storage disease | |
| EP4166672A1 (en) | A novel method for purification of protein- or peptide-based capsules | |
| KR20150129873A (ko) | 유전체 약물 전달용 나노입자 및 이의 제조방법 | |
| WO2024079361A1 (en) | A PROTEIN- OR PEPTIDE-BASED CAPSULE (PPC), PREFERABLY A VLP, LOADED WITH A MESSENGER RNA (mRNA) AND A METHOD OF PRODUCTION AND PURIFICATION THEREOF | |
| EP4651883A1 (en) | Pharmaceutical formulations of gene delivery vehicles | |
| Valentin | Silk fibroin hydrogels and films for neurological applications |