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19 条记录 (耗时 0.022 秒)

    Attenuation of Encephalitogenic Alphavirus and Uses Thereof
    1.
    发明申请
    Attenuation of Encephalitogenic Alphavirus and Uses Thereof 有权
    脑炎病毒的衰减及其用途

    公开(公告)号：US20120100181A1

    公开(公告)日：2012-04-26

    申请号：US13284098

    申请日：2011-10-28

    申请人： Ilya V. Frolov ,  Elena Frolova ,  Scott C. Weaver

    发明人： Ilya V. Frolov ,  Elena Frolova ,  Scott C. Weaver

    IPC分类号： A61K39/12 ,  A61P37/04 ,  A61P31/14 ,  C12N7/04

    CPC分类号： C12N7/00 ,  A61K39/12 ,  A61K2039/5254 ,  C07K14/005 ,  C12N2770/36122 ,  C12N2770/36134 ,  C12N2770/36161

    摘要： The present invention is drawn to generating attenuated and less cytopathic forms of New World alphaviruses that can be used in immunogenic compositions as vaccines against both Old and New World alphaviruses. In this regard, the present invention discloses that the N-terminal, ˜35-aa-long peptide of VEEV, EEEV and, most likely, of WEEV capsid proteins plays the most critical role in the downregulation of cellular transcription and development of cytopathic effect. The identified, VEEV-specific peptide, CVEE30-68, includes two domains with distinguished functions. The integrity of both domains determines not only the intracellular distribution of CVEE, but is also essential for direct capsid function in the inhibition of transcription. The replacement of the N-terminal fragment of CVEE by its SINV-specific counterpart in VEEV TC-83 genome does not affect virus replication in vitro, but makes it less cytopathic and more attenuated in vivo.

    摘要翻译： 本发明被用于产生减毒和较少细胞病变形式的新世界甲病毒，其可用于免疫原性组合物中作为针对旧世界和新世界甲病毒的疫苗。 在这方面，本发明公开了VEEV，EEEV和最有可能的WEEV衣壳蛋白的N-末端，〜35-aa长肽在细胞转录的下调和细胞病变效应的发展中起着最关键的作用 。 鉴定的VEEV特异性肽CVEE30-68包括具有显着功能的两个结构域。 两个结构域的完整性不仅决定了CVEE的细胞内分布，而且对抑制转录的直接衣壳功能也是至关重要的。 VEEV TC-83基因组中由其特定于SINV特异的对应物替代CVEE的N-末端片段不影响体外病毒复制，但使体内细胞致病性降低并减弱。

    Attenuation of encephalitogenic alphavirus and uses thereof
    2.
    发明申请
    Attenuation of encephalitogenic alphavirus and uses thereof 审中-公开
    脑炎病毒的减毒及其用途

    公开(公告)号：US20100015179A1

    公开(公告)日：2010-01-21

    申请号：US12228710

    申请日：2008-08-15

    申请人： Ilya V. Frolov ,  Elena Frolova ,  Scott C. Weaver

    发明人： Ilya V. Frolov ,  Elena Frolova ,  Scott C. Weaver

    IPC分类号： A61K39/12 ,  C12N7/04 ,  A61P31/12

    CPC分类号： C12N7/00 ,  A61K39/12 ,  A61K2039/5254 ,  C07K14/005 ,  C12N2770/36122 ,  C12N2770/36134 ,  C12N2770/36161

    摘要： The present invention is drawn to generating attenuated and less cytopathic forms of New World alphaviruses that can be used in immunogenic compositions as vaccines against both Old and New World alphaviruses. In this regard, the present invention discloses that the N-terminal, ˜35-aa-long peptide of VEEV, EEEV and, most likely, of WEEV capsid proteins plays the most critical role in the downregulation of cellular transcription and development of cytopathic effect. The identified, VEEV-specific peptide, CVEE30-68, includes two domains with distinguished functions. The integrity of both domains determines not only the intracellular distribution of CVEE, but is also essential for direct capsid function in the inhibition of transcription. The replacement of the N-terminal fragment of CVEE by its SINV-specific counterpart in VEEV TC-83 genome does not affect virus replication in vitro, but makes it less cytopathic and more attenuated in vivo.

    摘要翻译： 本发明被用于产生减毒和较少细胞病变形式的新世界甲病毒，其可用于免疫原性组合物中作为针对旧世界和新世界甲病毒的疫苗。 在这方面，本发明公开了VEEV，EEEV和最有可能的WEEV衣壳蛋白的N末端〜35-aa长肽在细胞转录的下调和细胞病变效应的发展中起着最关键的作用 。 鉴定的VEEV特异性肽CVEE30-68包括具有显着功能的两个结构域。 两个结构域的完整性不仅决定了CVEE的细胞内分布，而且对抑制转录的直接衣壳功能也是至关重要的。 VEEV TC-83基因组中由其特定于SINV特异的对应物替代CVEE的N-末端片段不影响体外病毒复制，但使体内细胞致病性降低并减弱。

    Attenuation of encephalitogenic alphavirus and uses thereof
    5.
    发明授权
    Attenuation of encephalitogenic alphavirus and uses thereof 有权
    脑炎病毒的减毒及其用途

    公开(公告)号：US08614082B2

    公开(公告)日：2013-12-24

    申请号：US13284098

    申请日：2011-10-28

    申请人： Ilya V. Frolov ,  Elena Frolova ,  Scott C. Weaver

    发明人： Ilya V. Frolov ,  Elena Frolova ,  Scott C. Weaver

    IPC分类号： C12N7/04 ,  A61K39/12

    CPC分类号： C12N7/00 ,  A61K39/12 ,  A61K2039/5254 ,  C07K14/005 ,  C12N2770/36122 ,  C12N2770/36134 ,  C12N2770/36161

    摘要： The present invention is drawn to generating attenuated and less cytopathic forms of New World alphaviruses that can be used in immunogenic compositions as vaccines against both Old and New World alphaviruses. In this regard, the present invention discloses that the N-terminal, ˜35-aa-long peptide of VEEV, EEEV and, most likely, of WEEV capsid proteins plays the most critical role in the downregulation of cellular transcription and development of cytopathic effect. The identified, VEEV-specific peptide, CVEE30-68, includes two domains with distinguished functions. The integrity of both domains determines not only the intracellular distribution of CVEE, but is also essential for direct capsid function in the inhibition of transcription. The replacement of the N-terminal fragment of CVEE by its SINV-specific counterpart in VEEV TC-83 genome does not affect virus replication in vitro, but makes it less cytopathic and more attenuated in vivo.

    摘要翻译： 本发明被用于产生减毒和较少细胞病变形式的新世界甲病毒，其可用于免疫原性组合物中作为针对旧世界和新世界甲病毒的疫苗。 在这方面，本发明公开了VEEV，EEEV和最有可能的WEEV衣壳蛋白的N末端〜35-aa长肽在细胞转录的下调和细胞病变效应的发展中起着最关键的作用 。 鉴定的VEEV特异性肽CVEE30-68包括具有显着功能的两个结构域。 两个结构域的完整性不仅决定了CVEE的细胞内分布，而且对抑制转录的直接衣壳功能也是至关重要的。 VEEV TC-83基因组中由其特定于SINV特异的对应物替代CVEE的N-末端片段不影响体外病毒复制，但使体内细胞致病性降低并减弱。

    Venezuelan equine encephalitis virus replicons with adaptive mutations in the genome and uses thereof
    7.
    发明申请
    Venezuelan equine encephalitis virus replicons with adaptive mutations in the genome and uses thereof 有权
    委内瑞兰马脑炎病毒复制子与基因组中的适应性突变及其用途

    公开(公告)号：US20060251678A1

    公开(公告)日：2006-11-09

    申请号：US11227671

    申请日：2005-09-14

    申请人： Ilya Frolov ,  Elena Frolova

    发明人： Ilya Frolov ,  Elena Frolova

    IPC分类号： A61K39/395 ,  A61K39/12

    CPC分类号： C12N7/00 ,  C12N2770/36121 ,  C12N2770/36143

    摘要： The present invention provides a Venezuelan equine encephalitis virus replicon RNA useful in the development of stable lines of mammalian, avian and insect cells in which these replicons will persistently replicate. Venezuelan equine encephalitis (VEE) virus replicons contain a number of unique adaptive mutations that make the replicons noncytopathic. The replicons remain resistant to IFN-α/β. Replicon replication leads to high-level production of heterologous proteins, which are encoded by the replicons' genome and are under the control of a viral subgenomic promoter. Also provided are methods of screening for inhibitory compounds of Venezuelan equine encephalitis virus replication and eastern equine encephalitis virus replication.

    摘要翻译： 本发明提供了一种可用于发展哺乳动物，禽和昆虫细胞的稳定系的委内瑞兰马脑炎病毒复制子RNA，其中这些复制子将持续复制。 委内瑞兰马脑炎（VEE）病毒复制子包含许多独特的适应性突变，使复制子非细胞病变。 复制子对IFN-α/β仍然具有抗性。 复制子复制导致异源蛋白质的高水平生产，其由复制子基因组编码并在病毒亚基因组启动子的控制之下。 还提供了筛选委内瑞兰马脑炎病毒复制和东马脑炎病毒复制的抑制性化合物的方法。

    Venezuelan equine encephalitis virus replicons with adaptive mutations in the genome and uses thereof
    9.
    发明授权
    Venezuelan equine encephalitis virus replicons with adaptive mutations in the genome and uses thereof 有权
    委内瑞兰马脑炎病毒复制子与基因组中的适应性突变及其用途

    公开(公告)号：US07332322B2

    公开(公告)日：2008-02-19

    申请号：US11227671

    申请日：2005-09-14

    申请人： Ilya Frolov ,  Elena Frolova

    发明人： Ilya Frolov ,  Elena Frolova

    IPC分类号： C12N7/04 ,  C12N15/86 ,  C12P21/04 ,  C12P19/34 ,  C12Q1/68

    CPC分类号： C12N7/00 ,  C12N2770/36121 ,  C12N2770/36143

    摘要： The present invention provides a Venezuelan equine encephalitis virus replicon RNA useful in the development of stable lines of mammalian, avian and insect cells in which these replicons will persistently replicate. Venezuelan equine encephalitis (VEE) virus replicons contain a number of unique adaptive mutations that make the replicons noncytopathic. The replicons remain resistant to IFN-α/β. Replicon replication leads to high-level production of heterologous proteins, which are encoded by the replicons' genome and are under the control of a viral subgenomic promoter. Also provided are methods of screening for inhibitory compounds of Venezuelan equine encephalitis virus replication and eastern equine encephalitis virus replication.

    摘要翻译： 本发明提供了一种可用于发展哺乳动物，禽和昆虫细胞的稳定系的委内瑞兰马脑炎病毒复制子RNA，其中这些复制子将持续复制。 委内瑞兰马脑炎（VEE）病毒复制子包含许多独特的适应性突变，使复制子非细胞病变。 复制子对IFN-α/β仍然具有抗性。 复制子复制导致异源蛋白质的高水平生产，其由复制子基因组编码并在病毒亚基因组启动子的控制下。 还提供了筛选委内瑞兰马脑炎病毒复制和东马脑炎病毒复制的抑制性化合物的方法。