RU2018131783A - Транс-реплицирующая рнк - Google Patents
Транс-реплицирующая рнк Download PDFInfo
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- RU2018131783A RU2018131783A RU2018131783A RU2018131783A RU2018131783A RU 2018131783 A RU2018131783 A RU 2018131783A RU 2018131783 A RU2018131783 A RU 2018131783A RU 2018131783 A RU2018131783 A RU 2018131783A RU 2018131783 A RU2018131783 A RU 2018131783A
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- Prior art keywords
- alphavirus
- replicase
- rna
- expression
- replication
- Prior art date
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- 241000710929 Alphavirus Species 0.000 claims 29
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 28
- 108010026228 mRNA guanylyltransferase Proteins 0.000 claims 25
- 230000010076 replication Effects 0.000 claims 13
- 108700026244 Open Reading Frames Proteins 0.000 claims 8
- 108090000623 proteins and genes Proteins 0.000 claims 7
- 102000004169 proteins and genes Human genes 0.000 claims 7
- 101710172711 Structural protein Proteins 0.000 claims 3
- 108091027544 Subgenomic mRNA Proteins 0.000 claims 3
- 238000000034 method Methods 0.000 claims 3
- 108091026898 Leader sequence (mRNA) Proteins 0.000 claims 2
- 108091034057 RNA (poly(A)) Proteins 0.000 claims 2
- 108091036066 Three prime untranslated region Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 241001502567 Chikungunya virus Species 0.000 claims 1
- 108091026890 Coding region Proteins 0.000 claims 1
- 108020004414 DNA Proteins 0.000 claims 1
- 108060004795 Methyltransferase Proteins 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 241000710960 Sindbis virus Species 0.000 claims 1
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 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
- C12N15/63—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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
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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
- C12N15/64—General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host
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- C12N15/09—Recombinant DNA-technology
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- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N9/1241—Nucleotidyltransferases (2.7.7)
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- C12Y207/07—Nucleotidyltransferases (2.7.7)
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- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
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- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36141—Use of virus, viral particle or viral elements as a vector
- C12N2770/36143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Claims (42)
1. Система, содержащая:
конструкцию РНК для экспрессии альфавирусной репликазы,
РНК-репликон, который может быть реплицирован репликазой in trans,
причем конструкция РНК для экспрессии альфавирусной репликазы содержит 5’-кэп для трансляции репликазы.
2. Система по п. 1, в которой 5’-кэп представляет собой природный 5’-кэп или аналог 5’-кэпа.
3. Система по п. 1 или 2, в которой конструкция РНК для экспрессии альфавирусной репликазы не содержит элемент участка внутренней посадки рибосомы (IRES) для трансляции репликазы.
4. Система по любому из пп. 1-3, в которой конструкция РНК для экспрессии альфавирусной репликазы содержит:
(1) 5' UTR,
(2) открытую рамку считывания, кодирующую репликазу, и
(3) 3' UTR.
5. Система по п. 4, в которой 5' UTR и/или 3' UTR являются ненативными для альфавируса, из которого получена репликаза.
6. Система по любому из пп. 1-5, в которой открытая рамка считывания, кодирующая альфавирусную репликазу, содержит кодирующую область(-и) для неструктурных белков, необходимых для репликации РНК.
7. Система по любому из пп. 1-6, в которой конструкция РНК для экспрессии альфавирусной репликазы содержит 3' поли(А)-последовательность.
8. Система по любому из пп. 1-7, в которой конструкция РНК для экспрессии альфавирусной репликазы не может быть реплицирована репликазой.
9. Система по любому из пп. 1-8, в которой РНК-репликон содержит:
(1) 5' репликационную последовательность распознавания альфавируса и
(2) 3' репликационную последовательность распознавания альфавируса.
10. Система по п. 9, в которой 5' репликационная последовательность распознавания альфавируса и 3' репликационная последовательность распознавания альфавируса направляют репликацию РНК-репликона в присутствии репликазы.
11. Система по п. 9 или 10, в которой 5' репликационная последовательность распознавания альфавируса и 3' репликационная последовательность распознавания альфавируса являются нативными для альфавируса, из которого получена репликаза.
12. Система по любому из пп. 1-11, в которой РНК-репликон содержит гетерологичную нуклеиновую кислоту.
13. Система по любому из пп. 1-12, в которой РНК-репликон содержит открытую рамку считывания, кодирующую представляющий интерес белок.
14. Система по п. 13, в которой открытая рамка считывания, кодирующая представляющий интерес белок, является ненативной для альфавируса, из которого получена репликаза.
15. Система по п. 13 или 14, в которой экспрессия открытой рамки считывания, кодирующей представляющий интерес белок, находится под контролем субгеномного промотора.
16. Система по п. 15, в которой субгеномный промотор является нативным для альфавируса, из которого получена репликаза.
17. Система по п. 15 или 16, в которой субгеномный промотор представляет собой промотор структурного белка альфавируса.
18. Система по любому из пп. 1-17, в которой РНК-репликон содержит 3' поли(А)-последовательность.
19. Система по любому из пп. 1-18, в которой РНК-репликон содержит 5’-кэп.
20. Система по любому из пп. 1-19, в которой конструкция РНК для экспрессии альфавирусной репликазы и/или РНК-репликон не содержит открытую рамку считывания, кодирующую интактный структурный белок альфавируса.
21. Система по любому из пп. 1-20, в которой альфавирус представляет собой вирус леса Семлики или вирус венесуэльского лошадиного энцефалита, или вирус Синдбис, или вирус Чикунгунья.
22. Конструкция РНК для экспрессии альфавирусной репликазы, содержащая 5’-кэп для трансляции репликазы.
23. ДНК, содержащая последовательность нуклеиновой кислоты, кодирующую конструкцию РНК для экспрессии альфавирусной репликазы, РНК-репликон или обе системы по любому из пп. 1-21.
24. Способ получения белка в клетке, предусматривающий следующие стадии:
(а) получение конструкции РНК для экспрессии альфавирусной репликазы,
(b) получение РНК-репликона, который может быть реплицирован репликазой in trans и содержит открытую рамку считывания, кодирующую белок, и
(c) инокуляция клетки смесью конструкции РНК для экспрессии альфавирусной репликазы и РНК-репликона,
причем конструкция РНК для экспрессии альфавирусной репликазы содержит 5’-кэп для трансляции репликазы.
25. Клетка, инокулированная по способу по п. 24.
26. Способ получения белка у субъекта, предусматривающий следующие стадии:
(а) получение конструкции РНК для экспрессии альфавирусной репликазы,
(b) получение РНК-репликона, который может быть реплицирован репликазой in trans и содержит открытую рамку считывания, кодирующую белок, и
(c) введение конструкции РНК для экспрессии альфавирусной репликазы и РНК-репликона субъекту,
причем конструкция РНК для экспрессии альфавирусной репликазы содержит 5’-кэп для трансляции репликазы.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EPPCT/EP2016/056160 | 2016-03-21 | ||
| PCT/EP2016/056160 WO2017162265A1 (en) | 2016-03-21 | 2016-03-21 | Trans-replicating rna |
| PCT/EP2017/055813 WO2017162461A1 (en) | 2016-03-21 | 2017-03-13 | Trans-replicating rna |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2018131783A true RU2018131783A (ru) | 2020-04-22 |
| RU2018131783A3 RU2018131783A3 (ru) | 2020-07-14 |
| RU2752580C2 RU2752580C2 (ru) | 2021-07-29 |
Family
ID=55586324
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018131783A RU2752580C2 (ru) | 2016-03-21 | 2017-03-13 | Транс-реплицирующая рнк |
Country Status (26)
| Country | Link |
|---|---|
| US (2) | US12338448B2 (ru) |
| EP (2) | EP3964584A1 (ru) |
| JP (2) | JP7105193B2 (ru) |
| KR (1) | KR102441725B1 (ru) |
| CN (2) | CN115386596A (ru) |
| AU (1) | AU2017236240B2 (ru) |
| BR (1) | BR112018068391A2 (ru) |
| CY (1) | CY1124689T1 (ru) |
| DK (1) | DK3433368T3 (ru) |
| ES (1) | ES2896927T3 (ru) |
| HR (1) | HRP20211715T1 (ru) |
| HU (1) | HUE058889T2 (ru) |
| IL (1) | IL261327B2 (ru) |
| LT (1) | LT3433368T (ru) |
| MA (1) | MA44479B1 (ru) |
| MD (1) | MD3433368T2 (ru) |
| MX (1) | MX2018011384A (ru) |
| PL (1) | PL3433368T3 (ru) |
| PT (1) | PT3433368T (ru) |
| RS (1) | RS62543B1 (ru) |
| RU (1) | RU2752580C2 (ru) |
| SG (1) | SG11201807378SA (ru) |
| SI (1) | SI3433368T1 (ru) |
| SM (1) | SMT202100634T1 (ru) |
| WO (2) | WO2017162265A1 (ru) |
| ZA (2) | ZA201805520B (ru) |
Families Citing this family (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4218805A1 (en) | 2015-07-21 | 2023-08-02 | ModernaTX, Inc. | Infectious disease vaccines |
| US11364292B2 (en) | 2015-07-21 | 2022-06-21 | Modernatx, Inc. | CHIKV RNA vaccines |
| WO2017070624A1 (en) | 2015-10-22 | 2017-04-27 | Modernatx, Inc. | Tropical disease vaccines |
| CN111094549B (zh) * | 2017-09-13 | 2024-11-01 | 生物技术公司 | 用于将体细胞重编程的rna复制子 |
| JP7389741B2 (ja) * | 2017-09-13 | 2023-11-30 | バイオエヌテック セル アンド ジーン セラピーズ ゲーエムベーハー | T細胞受容体または人工t細胞受容体を発現するためのrnaレプリコン |
| WO2019055807A1 (en) | 2017-09-14 | 2019-03-21 | Modernatx, Inc. | RNA VACCINES AGAINST ZIKA VIRUS |
| US10736957B2 (en) | 2017-12-19 | 2020-08-11 | President And Fellows Of Harvard College | Enhanced immunogenicity of mRNA with co-encoded adjuvant sequences |
| US12070495B2 (en) | 2019-03-15 | 2024-08-27 | Modernatx, Inc. | HIV RNA vaccines |
| CN114072513A (zh) * | 2019-06-27 | 2022-02-18 | Emd密理博公司 | 用表达永生化蛋白的自我复制型rna载体的细胞扩增 |
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