Venezuelan equine encephalitis virus replicons with adaptive mutations in the genome and uses thereof
    1.
    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

    IPC分类号: A61K39/395 A61K39/12

    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
    3.
    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

    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。

    Pseudoinfectious Flavivirus and Uses Thereof
    7.
    发明申请
    Pseudoinfectious Flavivirus and Uses Thereof 审中-公开
    伪感染黄病毒及其用途

    公开(公告)号:US20130023031A1

    公开(公告)日:2013-01-24

    申请号:US13561002

    申请日:2012-07-28

    IPC分类号: C12N7/00 C12N7/01 C12N5/10

    摘要: The present invention discloses a replication-deficient pseudoinfective virus belonging to the Flaviviridae family that lack the capsid gene, where the replication-deficient pseudoinfective virus propagates only in cells expressing the capsid or capsid, prM and envelope protein of the flavivirus. The present also discloses the method of producing such viruses on a large scale and the use of these pseudoinfective viruses as vaccines for preventing diseases caused by infections of humans or animals by the viruses belonging to this family.

    摘要翻译: 本发明公开了属于黄病毒科的复制缺陷型假性感染病毒,其缺乏衣壳基因,其中复制缺陷型假病毒病毒仅在表达黄病毒的衣壳或衣壳,prM和包膜蛋白的细胞中繁殖。 本发明还公开了大规模生产这种病毒的方法,以及这些假感染性病毒作为疫苗用于预防由该家族的病毒感染人或动物引起的疾病的疫苗。

    Pseudoinfectious flavivirus and uses thereof
    8.
    发明授权
    Pseudoinfectious flavivirus and uses thereof 有权
    伪感染黄病毒及其用途

    公开(公告)号:US08252574B2

    公开(公告)日:2012-08-28

    申请号:US11711532

    申请日:2007-02-27

    IPC分类号: C12N7/00 A61K39/12

    摘要: The present invention discloses a replication-deficient pseudoinfective virus belonging to the Flaviviridae family that lack the capsid gene, where the replication-deficient pseudoinfective virus propagates only in cells expressing the capsid or capsid, prM and envelope protein of the flavivirus. The present also discloses the method of producing such viruses on a large scale and the use of these pseudoinfective viruses as vaccines for preventing diseases caused by infections of humans or animals by the viruses belonging to this family.

    摘要翻译: 本发明公开了属于黄病毒科的复制缺陷型假性感染病毒,其缺乏衣壳基因,其中复制缺陷型假病毒病毒仅在表达黄病毒的衣壳或衣壳,prM和包膜蛋白的细胞中繁殖。 本发明还公开了大规模生产这种病毒的方法,以及这些假感染性病毒作为疫苗用于预防由该家族的病毒感染人或动物引起的疾病的疫苗。

    Large scale production of packaged alphavirus replicons
    9.
    发明授权
    Large scale production of packaged alphavirus replicons 有权
    大规模生产包装的甲病毒复制子

    公开(公告)号:US06943015B2

    公开(公告)日:2005-09-13

    申请号:US10735046

    申请日:2003-12-12

    摘要: Large-scale packaging of alphavirus replicons is accomplished by co-transfecting host cells with three RNA molecules: (1) an alphavirus replicon comprising a sequence encoding a heterologous protein; (2) a helper RNA encoding a capsid protein and (3) a helper RNA encoding two alphavirus glycoproteins. The helper RNAs contain cis-acting elements that allow efficient replication of the helper RNAs and their packaging into viral particles as well as packaging of replicon genomes. These populations of viral particles can be propagated at high titers in cell culture by infecting cells at high multiplicity. Propagation of packaged replicons at an escalating scale is useful for large-scale production of recombinant proteins and/or vaccine.

    摘要翻译: 通过用三个RNA分子共转染宿主细胞来实现甲病毒复制子的大规模包装:(1)包含编码异源蛋白质的序列的甲病毒复制子; (2)编码衣壳蛋白的辅助RNA和(3)编码两种甲病毒糖蛋白的辅助RNA。 辅助RNA包含顺式作用元件,其允许辅助RNA及其包装有效复制到病毒颗粒中以及复制子基因组的包装。 通过以高倍数感染细胞,这些病毒颗粒群可以在细胞培养中以高效价繁殖。 包装复制品在不断扩大的规模下的传播对于大规模生产重组蛋白和/或疫苗是有用的。

    Attenuation of Encephalitogenic Alphavirus and Uses Thereof
    10.
    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

    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。