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公开(公告)号：US20170354727A1
公开(公告)日：2017-12-14
申请号：US15684355
申请日：2017-08-23
申请人： The Government of the USA as represented by the Secretary of the Dept. of Health and Human Service
IPC分类号： A61K39/108 , C12N15/67 , C12N7/00 , A61K39/00 , C07K14/245
CPC分类号： A61K39/0258 , A61K39/00 , A61K2039/522 , A61K2039/5254 , C07K14/245 , C12N7/00 , C12N15/67 , C12N2710/16162 , C12N2710/16662 , C12N2710/16762 , C12N2760/16162 , C12N2760/18462 , C12N2760/18562 , C12N2770/20062 , C12N2770/24162 , C12N2770/32162 , C12N2770/32762 , C12N2770/36262 , Y02A50/466 , Y02A50/472 , Y02A50/476
摘要： Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.
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公开(公告)号：US09476032B2
公开(公告)日：2016-10-25
申请号：US12594173
申请日：2008-03-31
申请人： Eckard Wimmer , Steve Skiena , Steffen Mueller , Bruce Futcher , Dimitris Papamichail , John Robert Coleman , Jeronimo Cello
发明人： Eckard Wimmer , Steve Skiena , Steffen Mueller , Bruce Futcher , Dimitris Papamichail , John Robert Coleman , Jeronimo Cello
CPC分类号： C12N7/00 , A61K39/13 , A61K39/145 , A61K2039/5254 , C07K14/005 , C12N2720/12361 , C12N2740/15061 , C12N2760/16061 , C12N2760/16121 , C12N2760/16134 , C12N2760/16162 , C12N2770/20061 , C12N2770/24161 , C12N2770/32061 , C12N2770/32621 , C12N2770/32634 , C12N2770/32661 , C12N2770/32662 , C12N2770/32671 , C12N2770/32721 , C12N2770/32761 , C12N2770/32762 , Y02A50/386 , Y02A50/388 , Y02A50/466
摘要： This invention provides an attenuated virus which comprises a modified viral genome containing nucleotide substitutions engineered in multiple locations in the genome, wherein the substitutions introduce synonymous deoptimized codons into the genome. The instant attenuated virus may be used in a vaccine composition for inducing a protective immune response in a subject. The invention also provides a method of synthesizing the instant attenuated virus. Further, this invention further provides a method for preventing a subject from becoming afflicted with a virus-associated disease comprising administering to the subject a prophylactically effective dose of a vaccine composition comprising the instant attenuated virus.
摘要翻译： 本发明提供了一种减毒病毒，其包含经修饰的病毒基因组，其含有在基因组中多个位置工程改造的核苷酸取代，其中所述取代引入同义脱酮密码子进入基因组。 本发明的减毒病毒可用于疫苗组合物中以在受试者中诱导保护性免疫应答。 本发明还提供了合成即时减毒病毒的方法。 此外，本发明进一步提供了一种防止受试者患有病毒相关疾病的方法，包括向受试者施用预防有效剂量的包含即时减毒病毒的疫苗组合物。
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公开(公告)号：US20040142477A1
公开(公告)日：2004-07-22
申请号：US10773601
申请日：2004-02-06
IPC分类号： A01H001/00 , C12N015/82 , C12N015/87 , C12N005/04
CPC分类号： C12N15/1137 , C07K14/005 , C07K14/415 , C07K14/70571 , C12N9/00 , C12N9/0059 , C12N9/0071 , C12N9/0083 , C12N9/1074 , C12N9/1085 , C12N9/14 , C12N9/16 , C12N9/18 , C12N9/20 , C12N9/6459 , C12N9/78 , C12N9/84 , C12N15/8203 , C12N15/8216 , C12N15/8218 , C12N15/8249 , C12N15/825 , C12N15/8289 , C12N15/86 , C12N2710/22043 , C12N2710/22062 , C12N2750/12043 , C12N2770/00022 , C12N2770/00043 , C12N2770/00051 , C12N2770/32643 , C12N2770/32662 , C12N2770/32722 , C12N2770/32743 , C12N2770/32762 , C12N2770/36143 , C12N2770/36162 , C12N2799/021 , C12N2810/609 , C12P41/003 , C12Y114/18001 , C12Y302/01031 , C12Y304/21069 , G01N2333/4353
摘要： The invention provides novel genetic constructions for the expression of inhibitory RNA in the cytoplasm of eukaryotic cells. The inhibitory RNA may be an anti-sense RNA or a co-suppressor RNA, and functions to reduce the expression of a gene of interest in the target cell. The genetic constructions of the invention are capable of replicating in the cytoplasm of a eukaryotic cell and comprise a promoter region in functional combination with an encoding polynucleotide. The genetic constructions may be designed so as to replicate in the cytoplasm of plant cells, yeast cells, and mammalian cells. When the eukaryotic cell of interest is a plant cell, the genetic construction is preferably derived from a plant RNA virus. Plant RNA virus derived genetic constructions may employ a plant virus subgenomic promoter, including subgenomic promoters from tobamoviruses in functional combination with the RNA encoding region. In a preferred embodiment of the invention, plant cells are induced to produce elevated levels of the carotenoid phytoene. The elevated levels of phytoene are achieved by inhibiting the expression of the enzyme phytoene desaturase using the vectors of the invention.
摘要翻译： 本发明提供了用于在真核细胞的细胞质中表达抑制性RNA的新型遗传构建体。 抑制性RNA可以是反义RNA或共抑制RNA，并且起减少目标细胞中目的基因表达的作用。 本发明的遗传结构能够在真核细胞的细胞质中复制并且包含与编码多核苷酸的功能性组合的启动子区。 遗传结构可以设计成在植物细胞，酵母细胞和哺乳动物细胞的细胞质中复制。 当感兴趣的真核细胞是植物细胞时，遗传构建优选衍生自植物RNA病毒。 植物RNA病毒衍生的遗传结构可以使用植物病毒亚基因组启动子，包括与RNA编码区域功能组合的来自烟草花叶病毒的亚基因组启动子。 在本发明的一个优选实施方案中，诱导植物细胞产生升高水平的类胡萝卜素八氢番茄红素。 通过使用本发明的载体抑制酶八氢番茄红素去饱和酶的表达来实现提高的八氢番茄聚糖水平。
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公开(公告)号：US5889190A
公开(公告)日：1999-03-30
申请号：US480432
申请日：1995-06-07
申请人： Jon Donson , William O. Dawson , George L. Grantham , Thomas H. Turpen , Ann Myers Turpen , Stephen J. Garger , Laurence K. Grill
发明人： Jon Donson , William O. Dawson , George L. Grantham , Thomas H. Turpen , Ann Myers Turpen , Stephen J. Garger , Laurence K. Grill
IPC分类号： C07K14/08 , C07K14/095 , C07K14/415 , C12N9/00 , C12N9/02 , C12N9/10 , C12N9/14 , C12N9/16 , C12N9/18 , C12N9/20 , C12N9/24 , C12N9/72 , C12N9/78 , C12N9/84 , C12N15/113 , C12N15/12 , C12N15/33 , C12N15/40 , C12N15/82 , C12N15/83 , C12N15/86 , C12P41/00 , A01H5/00
CPC分类号： C12Y114/18001 , C07K14/005 , C07K14/415 , C12N15/1137 , C12N15/8203 , C12N15/8216 , C12N15/8218 , C12N15/8249 , C12N15/825 , C12N15/8289 , C12N15/86 , C12N9/00 , C12N9/0059 , C12N9/0071 , C12N9/0083 , C12N9/1074 , C12N9/14 , C12N9/16 , C12N9/18 , C12N9/20 , C12N9/6459 , C12N9/78 , C12N9/84 , C12P41/003 , C12Y302/01031 , C12Y304/21069 , C12N2710/22043 , C12N2710/22062 , C12N2750/12043 , C12N2770/00022 , C12N2770/00043 , C12N2770/00051 , C12N2770/32643 , C12N2770/32662 , C12N2770/32722 , C12N2770/32743 , C12N2770/32762 , C12N2770/36122 , C12N2770/36143 , C12N2770/36162 , C12N2810/609
摘要： The present invention is directed to recombinant plant viral nucleic acids and to hosts infected thereby. The recombinant plant viral nucleic acids comprise a native plant viral subgenomic promoter, at least one non-native plant viral subgenomic promoter, a plant viral coat protein coding sequence, and optionally, at least one non-native nucleic acid sequence to be transcribed or expressed in the infected host plant. The recombinant plant viral nucleic acids are stable, capable of systemic infection and capable of stable transcription or expression in the plant host of the non-native nucleic acid sequences.
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公开(公告)号：US20230270833A1
公开(公告)日：2023-08-31
申请号：US18047395
申请日：2022-10-18
申请人： The Government of the USA as represented by the Secretary of the Dept. of Health and Human Services
IPC分类号： A61K39/108 , A61K39/00 , C07K14/245 , C12N15/67 , C12N7/00
CPC分类号： A61K39/0258 , A61K39/00 , C07K14/245 , C12N15/67 , C12N7/00 , A61K2039/522 , A61K2039/5254 , C12N2710/16162 , C12N2710/16662 , C12N2710/16762 , C12N2760/16162 , C12N2760/18462 , C12N2760/18562 , C12N2770/20062 , C12N2770/24162 , C12N2770/32162 , C12N2770/32762 , C12N2770/36262 , Y02A50/30
摘要： Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.
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公开(公告)号：US20170067030A1
公开(公告)日：2017-03-09
申请号：US15258584
申请日：2016-09-07
发明人： Eckard Wimmer , Steve Skiena , Steffen Mueller , Bruce Futcher , Dimitris Papamichail , John Robert Coleman , Jeronimo Cello
IPC分类号： C12N7/00 , A61K39/13 , A61K39/145 , C07K14/005
CPC分类号： C12N7/00 , A61K39/13 , A61K39/145 , A61K2039/5254 , C07K14/005 , C12N2720/12361 , C12N2740/15061 , C12N2760/16061 , C12N2760/16121 , C12N2760/16134 , C12N2760/16162 , C12N2770/20061 , C12N2770/24161 , C12N2770/32061 , C12N2770/32621 , C12N2770/32634 , C12N2770/32661 , C12N2770/32662 , C12N2770/32671 , C12N2770/32721 , C12N2770/32761 , C12N2770/32762 , Y02A50/386 , Y02A50/388 , Y02A50/466
摘要： This invention provides an attenuated virus which comprises a modified viral genome containing nucleotide substitutions engineered in multiple locations in the genome, wherein the substitutions introduce synonymous deoptimized codons into the genome. The instant attenuated virus may be used in a vaccine composition for inducing a protective immune response in a subject. The invention also provides a method of synthesizing the instant attenuated virus. Further, this invention further provides a method for preventing a subject from becoming afflicted with a virus-associated disease comprising administering to the subject a prophylactically effective dose of a vaccine composition comprising the instant attenuated virus.
摘要翻译： 本发明提供了一种减毒病毒，其包含经修饰的病毒基因组，其含有在基因组中多个位置工程改造的核苷酸取代，其中所述取代引入同义脱酮密码子进入基因组。 本发明的减毒病毒可用于疫苗组合物中以在受试者中诱导保护性免疫应答。 本发明还提供了合成即时减毒病毒的方法。 此外，本发明进一步提供了一种防止受试者患有病毒相关疾病的方法，包括向受试者施用预防有效剂量的包含即时减毒病毒的疫苗组合物。
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公开(公告)号：US20080118530A1
公开(公告)日：2008-05-22
申请号：US11576941
申请日：2005-10-07
申请人： Olen M. Kew , Cara C. Burns , Jing Shaw , Raymond Campagnoli , Jacqueline Quay
发明人： Olen M. Kew , Cara C. Burns , Jing Shaw , Raymond Campagnoli , Jacqueline Quay
CPC分类号： A61K39/0258 , A61K39/00 , A61K2039/522 , A61K2039/5254 , C07K14/245 , C12N7/00 , C12N15/67 , C12N2710/16162 , C12N2710/16662 , C12N2710/16762 , C12N2760/16162 , C12N2760/18462 , C12N2760/18562 , C12N2770/20062 , C12N2770/24162 , C12N2770/32162 , C12N2770/32762 , C12N2770/36262 , Y02A50/466 , Y02A50/472 , Y02A50/476
摘要： Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.
摘要翻译： 公开了产生具有降低的复制适应性的病原体的方法，以及使用该方法产生的减毒病原体。 在具体实例中，该方法包括对编码序列中的一个或多个密码子进行去优化，从而降低病原体的复制适应性。 还公开了将减毒病原体用作免疫原性组合物的方法。
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公开(公告)号：US20050204422A1
公开(公告)日：2005-09-15
申请号：US11129170
申请日：2005-05-13
IPC分类号： A01H5/00 , C07K14/08 , C07K14/095 , C07K14/415 , C07K14/705 , C12N1/19 , C12N5/10 , C12N9/00 , C12N9/02 , C12N9/10 , C12N9/14 , C12N9/16 , C12N9/18 , C12N9/20 , C12N9/24 , C12N9/72 , C12N9/78 , C12N9/84 , C12N15/09 , C12N15/113 , C12N15/12 , C12N15/40 , C12N15/53 , C12N15/82 , C12N15/83 , C12N15/86 , C12P21/04 , C12P41/00 , A01H1/00
CPC分类号： C12N15/1137 , C07K14/005 , C07K14/415 , C07K14/70571 , C12N9/00 , C12N9/0059 , C12N9/0071 , C12N9/0083 , C12N9/1074 , C12N9/1085 , C12N9/14 , C12N9/16 , C12N9/18 , C12N9/20 , C12N9/6459 , C12N9/78 , C12N9/84 , C12N15/8203 , C12N15/8216 , C12N15/8218 , C12N15/8249 , C12N15/825 , C12N15/8289 , C12N15/86 , C12N2710/22043 , C12N2710/22062 , C12N2750/12043 , C12N2770/00022 , C12N2770/00043 , C12N2770/00051 , C12N2770/32643 , C12N2770/32662 , C12N2770/32722 , C12N2770/32743 , C12N2770/32762 , C12N2770/36143 , C12N2770/36162 , C12N2799/021 , C12N2810/609 , C12P41/003 , C12Y114/18001 , C12Y302/01031 , C12Y304/21069 , G01N2333/4353
摘要： The invention provides novel genetic constructions for the expression of inhibitory RNA in the cytoplasm of eukaryotic cells. The inhibitory RNA may be an anti-sense RNA or a co-suppressor RNA, and functions to reduce the expression of a gene of interest in the target cell. The genetic constructions of the invention are capable of replicating in the cytoplasm of a eukaryotic cell and comprise a promoter region in functional combination with an encoding polynucleotide. The genetic constructions may be designed so as to replicate in the cytoplasm of plant cells, yeast cells, and mammalian cells. When the eukaryotic cell of interest is a plant cell, the genetic construction is preferably derived from a plant RNA virus. Plant RNA virus derived genetic constructions may employ a plant virus subgenomic promoter, including subgenomic promoters from tobamoviruses in functional combination with the RNA encoding region. In a preferred embodiment of the invention, plant cells are induced to produce elevated levels of the carotenoid phytoene. The elevated levels of phytoene are achieved by inhibiting the expression of the enzyme phytoene desaturase using the vectors of the invention.
摘要翻译： 本发明提供了用于在真核细胞的细胞质中表达抑制性RNA的新型遗传构建体。 抑制性RNA可以是反义RNA或共抑制RNA，并且起减少目标细胞中目的基因表达的作用。 本发明的遗传结构能够在真核细胞的细胞质中复制并且包含与编码多核苷酸的功能性组合的启动子区。 遗传结构可以设计成在植物细胞，酵母细胞和哺乳动物细胞的细胞质中复制。 当感兴趣的真核细胞是植物细胞时，遗传构建优选衍生自植物RNA病毒。 植物RNA病毒衍生的遗传结构可以使用植物病毒亚基因组启动子，包括与RNA编码区域功能组合的来自烟草花叶病毒的亚基因组启动子。 在本发明的一个优选实施方案中，诱导植物细胞产生升高水平的类胡萝卜素八氢番茄红素。 通过使用本发明的载体抑制酶八氢番茄红素去饱和酶的表达来实现提高的八氢番茄聚糖水平。
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公开(公告)号：US5922602A
公开(公告)日：1999-07-13
申请号：US260546
申请日：1994-06-16
申请人： Monto Hiroshi Kumagai , Guy Richard della-Cioppa , Jonathan Donson , Damon Alan Harvey , Laurence K. Grill
发明人： Monto Hiroshi Kumagai , Guy Richard della-Cioppa , Jonathan Donson , Damon Alan Harvey , Laurence K. Grill
IPC分类号： A01H5/00 , C07K14/08 , C07K14/095 , C07K14/415 , C07K14/705 , C12N1/19 , C12N5/10 , C12N9/00 , C12N9/02 , C12N9/10 , C12N9/14 , C12N9/16 , C12N9/18 , C12N9/20 , C12N9/24 , C12N9/72 , C12N9/78 , C12N9/84 , C12N15/09 , C12N15/113 , C12N15/12 , C12N15/40 , C12N15/53 , C12N15/82 , C12N15/83 , C12N15/86 , C12P21/04 , C12P41/00 , C12N15/63
CPC分类号： C12N15/1137 , C07K14/005 , C07K14/415 , C07K14/70571 , C12N15/8203 , C12N15/8216 , C12N15/8218 , C12N15/8249 , C12N15/825 , C12N15/8289 , C12N15/86 , C12N9/00 , C12N9/0059 , C12N9/0071 , C12N9/0083 , C12N9/1074 , C12N9/1085 , C12N9/14 , C12N9/16 , C12N9/18 , C12N9/20 , C12N9/6459 , C12N9/78 , C12N9/84 , C12P41/003 , C12Y114/18001 , C12Y302/01031 , C12Y304/21069 , C12N2710/22043 , C12N2710/22062 , C12N2750/12043 , C12N2770/00022 , C12N2770/00043 , C12N2770/00051 , C12N2770/32643 , C12N2770/32662 , C12N2770/32722 , C12N2770/32743 , C12N2770/32762 , C12N2770/36143 , C12N2770/36162 , C12N2799/021 , C12N2810/609 , G01N2333/4353
摘要： The invention provides novel genetic constructions for the expression of inhibitory RNA in the cytoplasm of eukaryotic cells. The inhibitory RNA may be an anti-sense RNA or a co-suppressor RNA, and functions to reduce the expression of a gene of interest in the target cell. The genetic constructions of the invention are capable of replicating in the cytoplasm of a eukaryotic cell and comprise a promoter region in functional combination with an encoding polynucleotide. The genetic constructions may be designed so as to replicate in the cytoplasm of plant cells, yeast cells, and mammalian cells. When the eukaryotic cell of interest is a plant cell, the genetic construction is preferably derived from a plant RNA virus. Plant RNA virus derived genetic constructions may employ a plant virus subgenomic promoter, including subgenomic promoters from tobamoviruses in functional combination with the RNA encoding region. In a preferred embodiment of the invention, plant cells are induced to produce elevated levels of the carotenoid phytoene. The elevated levels of phytoene are achieved by inhibiting the expression of the enzyme phytoene desaturase using the vectors of the invention.
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公开(公告)号：US07192740B2
公开(公告)日：2007-03-20
申请号：US10280725
申请日：2002-10-24
申请人： Jonathan Donson , William O. Dawson , George L. Grantham , Thomas H. Turpen , Ann Myers Turpen , Stephen J. Garger, Jr. , Laurence K. Grill
发明人： Jonathan Donson , William O. Dawson , George L. Grantham , Thomas H. Turpen , Ann Myers Turpen , Stephen J. Garger, Jr. , Laurence K. Grill
CPC分类号： C07K14/005 , C07K14/415 , C12N9/00 , C12N9/0059 , C12N9/0071 , C12N9/0083 , C12N9/1074 , C12N9/14 , C12N9/16 , C12N9/18 , C12N9/20 , C12N9/6459 , C12N9/78 , C12N9/84 , C12N15/1137 , C12N15/8203 , C12N15/8216 , C12N15/8218 , C12N15/8249 , C12N15/825 , C12N15/8289 , C12N15/86 , C12N2710/22043 , C12N2710/22062 , C12N2750/12043 , C12N2770/00022 , C12N2770/00043 , C12N2770/00051 , C12N2770/32643 , C12N2770/32662 , C12N2770/32722 , C12N2770/32743 , C12N2770/32762 , C12N2770/36122 , C12N2770/36143 , C12N2770/36162 , C12N2810/609 , C12N2830/00 , C12N2830/60 , C12P41/003 , C12Y114/18001 , C12Y302/01031 , C12Y304/21069
摘要： The present invention relates to a recombinant viral nucleic acid selected from a (+) sense, single stranded RNA virus possessing a native subgenomic promoter encoding for a first viral subgenomic promoter, a nucleic acid sequence that codes for a viral coat protein whose transcription is regulated by the first viral subgenomic promoter, a second viral subgenomic promoter and a second nucleic acid sequence whose transcription is regulated by the second viral subgenomic promoter. The first and second viral subgenomic promoters of the recombinant viral nucleic acid do not have homologous sequences relative to each other. The recombinant viral nucleic acid provides the particular advantage that it systemically transcribes the second nucleic acid in the host. Host organisms encompassed by the present invention include procaryotes and eucaryotes, particularly animals and plants. The present invention also relates to viruses containing the viral vectors which are infective, production cells which are capable of producing the viruses or parts thereof, a host infected by the viruses of the invention, the gene products produced by expression of the viral nucleic acids and a process for the production of a desired product by growing the infected hosts.
摘要翻译： 本发明涉及选自具有编码第一病毒亚基因组启动子的天然亚基因启动子的（+）有义单链RNA病毒的重组病毒核酸，编码转录调节的病毒外壳蛋白的核酸序列 通过第一病毒亚基因组启动子，第二病毒亚基因组启动子和其转录受第二病毒亚基因组启动子调控的第二核酸序列。 重组病毒核酸的第一和第二病毒亚基因组启动子相对于彼此不具有同源序列。 重组病毒核酸提供其系统地转录宿主中的第二核酸的特别优点。 本发明包括的宿主生物包括原核生物和真核生物，特别是动物和植物。 本发明还涉及含有感染性病毒载体的病毒，能够产生病毒或其部分的生产细胞，被本发明的病毒感染的宿主，通过表达病毒核酸产生的基因产物和 通过生长受感染的宿主来生产所需产品的方法。
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