RU2476595C2 - Способы упаковки олигонуклеотидов в вирусоподобные частицы рнк-содержащих бактериофагов - Google Patents
Способы упаковки олигонуклеотидов в вирусоподобные частицы рнк-содержащих бактериофагов Download PDFInfo
- Publication number
- RU2476595C2 RU2476595C2 RU2008151507/10A RU2008151507A RU2476595C2 RU 2476595 C2 RU2476595 C2 RU 2476595C2 RU 2008151507/10 A RU2008151507/10 A RU 2008151507/10A RU 2008151507 A RU2008151507 A RU 2008151507A RU 2476595 C2 RU2476595 C2 RU 2476595C2
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- Prior art keywords
- oligonucleotide
- seq
- bacteriophage
- temperature
- solution
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- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract 35
- 238000000034 method Methods 0.000 title claims abstract 31
- 239000002245 particle Substances 0.000 title claims abstract 13
- 241001515965 unidentified phage Species 0.000 title claims abstract 13
- 238000004806 packaging method and process Methods 0.000 title claims 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 claims abstract 20
- 239000002773 nucleotide Substances 0.000 claims abstract 5
- 125000003729 nucleotide group Chemical group 0.000 claims abstract 5
- 238000000746 purification Methods 0.000 claims abstract 2
- 101710132601 Capsid protein Proteins 0.000 claims 10
- 101710094648 Coat protein Proteins 0.000 claims 10
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 claims 10
- 101710125418 Major capsid protein Proteins 0.000 claims 10
- 101710141454 Nucleoprotein Proteins 0.000 claims 10
- 101710083689 Probable capsid protein Proteins 0.000 claims 10
- 102000004169 proteins and genes Human genes 0.000 claims 9
- 108090000623 proteins and genes Proteins 0.000 claims 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 6
- 210000000234 capsid Anatomy 0.000 claims 5
- 150000001768 cations Chemical class 0.000 claims 5
- 239000003795 chemical substances by application Substances 0.000 claims 5
- 238000005227 gel permeation chromatography Methods 0.000 claims 5
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical group C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims 4
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 4
- 239000007800 oxidant agent Substances 0.000 claims 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 3
- 239000004202 carbamide Substances 0.000 claims 3
- 238000011534 incubation Methods 0.000 claims 3
- 150000007523 nucleic acids Chemical group 0.000 claims 3
- 239000011734 sodium Substances 0.000 claims 3
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims 2
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims 2
- 241001534160 Escherichia virus Qbeta Species 0.000 claims 2
- 108091081548 Palindromic sequence Proteins 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims 2
- 229940029575 guanosine Drugs 0.000 claims 2
- 238000001338 self-assembly Methods 0.000 claims 2
- 239000011780 sodium chloride Substances 0.000 claims 2
- 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 1
- 241001672158 Acinetobacter phage AP205 Species 0.000 claims 1
- 241000709737 Enterobacteria phage GA Species 0.000 claims 1
- 241001261579 Enterobacteria phage M11 Species 0.000 claims 1
- 241001278075 Enterobacteria phage MX1 Species 0.000 claims 1
- 241001278054 Enterobacteria phage NL95 Species 0.000 claims 1
- 241000709747 Enterobacteria phage R17 Species 0.000 claims 1
- 241000709743 Enterobacteria phage SP Species 0.000 claims 1
- 241000709739 Enterobacteria phage f2 Species 0.000 claims 1
- 241000709738 Enterobacteria phage fr Species 0.000 claims 1
- 241000709744 Enterobacterio phage MS2 Species 0.000 claims 1
- 101710091045 Envelope protein Proteins 0.000 claims 1
- 108010024636 Glutathione Proteins 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 108010052285 Membrane Proteins Proteins 0.000 claims 1
- 102000018697 Membrane Proteins Human genes 0.000 claims 1
- 101710188315 Protein X Proteins 0.000 claims 1
- 241000709749 Pseudomonas phage PP7 Species 0.000 claims 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims 1
- 102100021696 Syncytin-1 Human genes 0.000 claims 1
- 230000004931 aggregating effect Effects 0.000 claims 1
- 230000002776 aggregation Effects 0.000 claims 1
- 238000004220 aggregation Methods 0.000 claims 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 230000001276 controlling effect Effects 0.000 claims 1
- 239000013256 coordination polymer Substances 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 229960003180 glutathione Drugs 0.000 claims 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 238000010979 pH adjustment Methods 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
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- 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
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- 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
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- 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
- C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
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- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5258—Virus-like particles
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
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- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2795/00—Bacteriophages
- C12N2795/00011—Details
- C12N2795/00034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2795/00—Bacteriophages
- C12N2795/00011—Details
- C12N2795/18011—Details ssRNA Bacteriophages positive-sense
- C12N2795/18111—Leviviridae
- C12N2795/18122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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- 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
- C12N2795/00—Bacteriophages
- C12N2795/00011—Details
- C12N2795/18011—Details ssRNA Bacteriophages positive-sense
- C12N2795/18111—Leviviridae
- C12N2795/18123—Virus like particles [VLP]
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Crystallography & Structural Chemistry (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81259206P | 2006-06-12 | 2006-06-12 | |
| US60/812,592 | 2006-06-12 | ||
| PCT/EP2006/069734 WO2007068747A1 (en) | 2005-12-14 | 2006-12-14 | Immunostimulatory nucleic acid packaged particles for the treatment of hypersensitivity |
| EPPCT/EP2006/069734 | 2006-12-14 | ||
| PCT/EP2007/005188 WO2007144150A1 (en) | 2006-06-12 | 2007-06-12 | Processes for packaging oligonucleotides into virus-like particles of rna bacteriophages |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2008151507A RU2008151507A (ru) | 2010-07-20 |
| RU2476595C2 true RU2476595C2 (ru) | 2013-02-27 |
Family
ID=40243628
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2008151507/10A RU2476595C2 (ru) | 2006-06-12 | 2007-06-12 | Способы упаковки олигонуклеотидов в вирусоподобные частицы рнк-содержащих бактериофагов |
Country Status (20)
| Country | Link |
|---|---|
| US (4) | US8541559B2 (enExample) |
| EP (2) | EP2530086B1 (enExample) |
| JP (2) | JP5437797B2 (enExample) |
| KR (1) | KR101552227B1 (enExample) |
| CN (1) | CN101466720B (enExample) |
| AU (1) | AU2007260236B2 (enExample) |
| BR (1) | BRPI0713651B1 (enExample) |
| CA (1) | CA2655108C (enExample) |
| DK (1) | DK2032592T3 (enExample) |
| ES (2) | ES2738986T3 (enExample) |
| IL (1) | IL195526A (enExample) |
| MX (1) | MX2008015529A (enExample) |
| NZ (1) | NZ573622A (enExample) |
| PL (1) | PL2032592T3 (enExample) |
| PT (1) | PT2032592E (enExample) |
| RU (1) | RU2476595C2 (enExample) |
| SG (1) | SG172696A1 (enExample) |
| SI (1) | SI2032592T1 (enExample) |
| WO (1) | WO2007144150A1 (enExample) |
| ZA (1) | ZA200810109B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2816533C2 (ru) * | 2018-04-09 | 2024-04-01 | Чекмейт Фармасьютикалс | Упаковка олигонуклеотидов в вирусоподобные частицы |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101052411B (zh) | 2004-10-05 | 2011-04-06 | 赛托斯生物技术公司 | Vlp-抗原偶联物及其作为疫苗的用途 |
| JP5437797B2 (ja) | 2006-06-12 | 2014-03-12 | サイトス バイオテクノロジー アーゲー | Ｒｎａバクテリオファージのウイルス様粒子にオリゴヌクレオチドをパッケージ化するための方法 |
| WO2008071774A1 (en) * | 2006-12-14 | 2008-06-19 | Cytos Biotechnology Ag | Purification process for coat protein of rna bacteriophages |
| US8088392B2 (en) * | 2007-06-18 | 2012-01-03 | Yunxu Cao | Capsid proteins and uses therefore |
| WO2010138192A2 (en) | 2009-05-27 | 2010-12-02 | Selecta Biosciences, Inc. | Nanocarriers possessing components with different rates of release |
| CN102905728B (zh) | 2010-05-26 | 2015-11-25 | 西莱克塔生物科技公司 | 具有不偶合的佐剂的纳米载体组合物 |
| KR20140041505A (ko) | 2011-04-29 | 2014-04-04 | 셀렉타 바이오사이언시즈, 인크. | 조절 b 세포 유도를 위한 관용원성 합성 나노운반체 |
| US20130028857A1 (en) | 2011-07-29 | 2013-01-31 | Selecta Biosciences, Inc. | Synthetic nanocarriers comprising polymers comprising multiple immunomodulatory agents |
| WO2015024992A2 (en) * | 2013-08-22 | 2015-02-26 | Cytos Biotechnology Ag | Treatment of asthma |
| SI3240801T1 (sl) | 2014-12-31 | 2021-04-30 | Checkmate Pharmaceuticals, Inc. | Kombinirana imunoterapija tumorja |
| US11000472B2 (en) | 2015-04-06 | 2021-05-11 | Lg Household & Health Care Ltd. | Soluble microneedle for delivering poorly-soluble drug |
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