CA2443258A1 - Replicons derived from positive strand rna virus genomes useful for the production of heterologous proteins - Google Patents
Replicons derived from positive strand rna virus genomes useful for the production of heterologous proteins Download PDFInfo
- Publication number
- CA2443258A1 CA2443258A1 CA002443258A CA2443258A CA2443258A1 CA 2443258 A1 CA2443258 A1 CA 2443258A1 CA 002443258 A CA002443258 A CA 002443258A CA 2443258 A CA2443258 A CA 2443258A CA 2443258 A1 CA2443258 A1 CA 2443258A1
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- protein
- rna
- virus
- positive strand
- dna
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Classifications
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- 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
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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
- 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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- 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
- A61P31/14—Antivirals for RNA viruses
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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
- A61K2039/53—DNA (RNA) vaccination
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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
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/32011—Picornaviridae
- C12N2770/32211—Cardiovirus, e.g. encephalomyocarditis virus
- C12N2770/32241—Use of virus, viral particle or viral elements as a vector
- C12N2770/32243—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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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
- C12N2820/00—Vectors comprising a special origin of replication system
- C12N2820/60—Vectors comprising a special origin of replication system from viruses
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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
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
- C12N2840/203—Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
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- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29251501P | 2001-05-23 | 2001-05-23 | |
| US60/292,515 | 2001-05-23 | ||
| PCT/IB2002/002810 WO2002095023A2 (en) | 2001-05-23 | 2002-05-23 | Replicons derived from positive strand rna virus genomes useful for the production of heterologous proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2443258A1 true CA2443258A1 (en) | 2002-11-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002443258A Abandoned CA2443258A1 (en) | 2001-05-23 | 2002-05-23 | Replicons derived from positive strand rna virus genomes useful for the production of heterologous proteins |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US20030077251A1 (https=) |
| EP (1) | EP1390517A2 (https=) |
| JP (1) | JP2005508610A (https=) |
| KR (1) | KR20040007567A (https=) |
| CN (1) | CN1575339A (https=) |
| AU (1) | AU2002339603A1 (https=) |
| CA (1) | CA2443258A1 (https=) |
| WO (1) | WO2002095023A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4157456A4 (en) * | 2020-05-29 | 2024-06-26 | Oncorus, Inc. | ENCAPSULATED RNA REPLIKONS AND METHODS OF USE |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20060017635A (ko) | 2003-06-05 | 2006-02-24 | 와이어쓰 홀딩스 코포레이션 | 베네쥬엘라 말 뇌염 바이러스 레플리콘 벡터 및파라믹소바이러스 단백질 항원을 포함하는 면역원성 조성물 |
| KR100788894B1 (ko) | 2005-12-09 | 2007-12-27 | 한국전자통신연구원 | 확대된 서비스 영역을 제공하는 직교 주파수 분할 다중방식의 무선 랜 송수신 시스템 및 그 방법 |
| US20100111873A1 (en) * | 2007-02-20 | 2010-05-06 | Russell Stephen J | Treating cancer with viral nucleic acid |
| CA2689108C (en) * | 2007-06-01 | 2015-04-14 | Universidad De Barcelona | Control for virus detection assays based on reverse-transcription polymerase chain reaction |
| EP2130912A1 (en) * | 2008-06-04 | 2009-12-09 | Institut für Viruskrankeiten und Immunprophylaxe | Pestivirus replicons providing an RNA-based viral vector system |
| KR101694559B1 (ko) * | 2008-09-24 | 2017-01-09 | 가부시키가이샤 리보믹 | Ｎｇｆ에 대한 압타머 및 이의 용도 |
| US9770463B2 (en) | 2010-07-06 | 2017-09-26 | Glaxosmithkline Biologicals Sa | Delivery of RNA to different cell types |
| EP2591114B1 (en) | 2010-07-06 | 2016-06-08 | GlaxoSmithKline Biologicals SA | Immunisation of large mammals with low doses of rna |
| MX342608B (es) | 2010-07-06 | 2016-10-06 | Novartis Ag * | Particulas de suministro similares a viriones para moleculas de arn de autorreplicacion. |
| ES2557382T3 (es) | 2010-07-06 | 2016-01-25 | Glaxosmithkline Biologicals Sa | Liposomas con lípidos que tienen un valor de pKa ventajoso para el suministro de ARN |
| ES2646669T3 (es) | 2010-07-06 | 2017-12-14 | Glaxosmithkline Biologicals Sa | Procedimientos de aumento de una respuesta inmunitaria mediante el suministro de ARN |
| LT4226941T (lt) | 2010-08-31 | 2025-01-10 | Glaxosmithkline Biologicals Sa | Pegilintos liposomos, skirtos imunogeną koduojančios rnr pristatymui |
| SI4043040T1 (sl) | 2010-08-31 | 2023-04-28 | Glaxosmithkline Biologicals Sa | Mali liposomi za dostavo imunogen-kodirajoče RNA |
| WO2012051211A2 (en) | 2010-10-11 | 2012-04-19 | Novartis Ag | Antigen delivery platforms |
| RU2013154295A (ru) | 2011-06-08 | 2015-07-20 | Шир Хьюман Дженетик Терапис, Инк. | КОМПОЗИЦИИ ЛИПИДНЫХ НАНОЧАСТИЦ И СПОСОБЫ ДЛЯ ДОСТАВКИ мРНК |
| ES2795110T3 (es) | 2011-06-08 | 2020-11-20 | Translate Bio Inc | Lípidos escindibles |
| EP4115875A1 (en) * | 2011-07-06 | 2023-01-11 | GlaxoSmithKline Biologicals S.A. | Liposomes having useful n:p ratio for delivery of rna molecules |
| EP2729165B1 (en) | 2011-07-06 | 2017-11-08 | GlaxoSmithKline Biologicals SA | Immunogenic combination compositions and uses thereof |
| CN114231562A (zh) * | 2021-12-15 | 2022-03-25 | 中国科学院武汉病毒研究所 | 一种表达荧光素酶基因的淋巴脉络丛脑膜炎病毒及其构建方法和应用 |
| CN114317563B (zh) * | 2021-12-17 | 2023-09-05 | 华南理工大学 | 提高基因表达的rna复制子及其应用 |
| WO2023221938A1 (zh) * | 2022-05-16 | 2023-11-23 | 上海行深生物科技有限公司 | 蛋白包裹自复制rna及其制备方法 |
| EP4703471A1 (en) * | 2023-04-25 | 2026-03-04 | Shinshu University | Method for controlling transcription and/or replication of vrna by influenza virus rdrp, and use of same |
Family Cites Families (3)
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|---|---|---|---|---|
| GB9125896D0 (en) * | 1991-12-05 | 1992-02-05 | Almond Jeffrey W | Bicistronic viruses |
| EP0702724A1 (en) * | 1993-06-03 | 1996-03-27 | Institut Pasteur | Mengovirus as a vector for expression of foreign polypeptides |
| US5811407A (en) * | 1997-02-19 | 1998-09-22 | The University Of North Carolina At Chapel Hill | System for the in vivo delivery and expression of heterologous genes in the bone marrow |
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2002
- 2002-05-22 US US10/152,040 patent/US20030077251A1/en not_active Abandoned
- 2002-05-23 CN CNA028104889A patent/CN1575339A/zh active Pending
- 2002-05-23 JP JP2002592486A patent/JP2005508610A/ja not_active Withdrawn
- 2002-05-23 US US10/478,434 patent/US20050118566A1/en not_active Abandoned
- 2002-05-23 CA CA002443258A patent/CA2443258A1/en not_active Abandoned
- 2002-05-23 AU AU2002339603A patent/AU2002339603A1/en not_active Abandoned
- 2002-05-23 WO PCT/IB2002/002810 patent/WO2002095023A2/en not_active Ceased
- 2002-05-23 KR KR10-2003-7014871A patent/KR20040007567A/ko not_active Withdrawn
- 2002-05-23 EP EP02743559A patent/EP1390517A2/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4157456A4 (en) * | 2020-05-29 | 2024-06-26 | Oncorus, Inc. | ENCAPSULATED RNA REPLIKONS AND METHODS OF USE |
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| JP2005508610A (ja) | 2005-04-07 |
| CN1575339A (zh) | 2005-02-02 |
| US20030077251A1 (en) | 2003-04-24 |
| WO2002095023A2 (en) | 2002-11-28 |
| EP1390517A2 (en) | 2004-02-25 |
| WO2002095023A3 (en) | 2003-05-08 |
| KR20040007567A (ko) | 2004-01-24 |
| US20050118566A1 (en) | 2005-06-02 |
| AU2002339603A1 (en) | 2002-12-03 |
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