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    Paramyxoviruses comprising modified transcription start sequence
    6.
    发明授权
    Paramyxoviruses comprising modified transcription start sequence 失效
    副粘病毒包括修饰的转录起始序列

    公开(公告)号：US07144579B2

    公开(公告)日：2006-12-05

    申请号：US09979908

    申请日：2001-11-28

    申请人： Yoshiyuki Nagai ,  Atsushi Kato ,  Mamoru Hasegawa ,  Makoto Inoue

    发明人： Yoshiyuki Nagai ,  Atsushi Kato ,  Mamoru Hasegawa ,  Makoto Inoue

    IPC分类号： C07H19/00 ,  C12N15/63 ,  C12N15/66 ,  A61K39/12 ,  A61K39/155

    CPC分类号： C07K14/005 ,  A61K48/00 ,  C12N15/86 ,  C12N2760/18822 ,  C12N2760/18843

    摘要： The present invention provides virus vectors of the family Paramyxoviridae in which the transcription start (S) sequence has been modified so as to modify the expression of genes located downstream thereof, a method for producing the vectors, and uses thereof. By measuring the transcription initiation efficiency of the S sequence of each gene carried by Sendai viruses (SeV), it was clarified that the S sequence of F gene has a significantly lower ability to promote transcription than the other three S sequences. When the S sequence of the F gene of wild type Sendai virus was substituted by the S sequence of the P/M/HN gene-type showing a high transcription initiation efficiency, the F gene of the resultant Sendai virus mutant and genes located downstream thereof show elevated expression levels. It was also revealed that this mutant proliferates more quickly than the wild type. The vectors of this invention are useful in elevating the expression of foreign genes and producing pharmaceutical compositions and vaccines. Furthermore, by lowering virus gene expression from virus vectors, it is possible to suppress transcription and/or replication and reduce cytotoxicity of the vector genome.

    摘要翻译： 本发明提供了副粘病毒科的病毒载体，其中已经修饰了转录起始（S）序列，以便修饰其下游的基因的表达，生成载体的方法及其用途。 通过测量仙台病毒（SeV）携带的每个基因的S序列的转录起始效率，阐明了F基因的S序列比其他三个S序列具有显着较低的促进转录能力。 当野生型仙台病毒的F基因的S序列被显示高转录起始效率的P / M / HN基因型的S序列取代时，得到的仙台病毒突变体的F基因和位于其下游的基因 显示升高的表达水平。 还显示，该突变体比野生型增殖更快。 本发明的载体可用于提高外源基因的表达并产生药物组合物和疫苗。 此外，通过降低来自病毒载体的病毒基因表达，可以抑制转录和/或复制并降低载体基因组的细胞毒性。

    AIDS virus vaccines using Sendai virus vector
    7.
    发明授权
    AIDS virus vaccines using Sendai virus vector 有权
    艾滋病病毒疫苗使用仙台病毒载体

    公开(公告)号：US08217019B2

    公开(公告)日：2012-07-10

    申请号：US12701303

    申请日：2010-02-05

    申请人： Munehide Kano ,  Tetsuro Matano ,  Atsushi Kato ,  Yoshiyuki Nagai ,  Mamoru Hasegawa

    发明人： Munehide Kano ,  Tetsuro Matano ,  Atsushi Kato ,  Yoshiyuki Nagai ,  Mamoru Hasegawa

    IPC分类号： A61K48/00 ,  C12N15/74 ,  A01N63/00

    CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/53 ,  A61K2039/543 ,  A61K2039/545 ,  A61K2039/57 ,  C12N2740/15034 ,  C12N2760/18843 ,  C12N2760/18871 ,  C12N2800/30

    摘要： The present invention provides a vaccine containing a Sendai virus vector encoding a virus protein of an immunodeficiency virus. By intranasally administering a Sendai virus encoding a virus protein of an immunodeficiency virus to a macaque monkey, the present inventors have succeeded in efficiently inducing protective immunity against an immunodeficiency virus. As a result of intranasal inoculation of vaccine, expression of an antigen protein mediated by Sendai virus vector was detected in intranasal mucous membrane and local lymph nodes and antigen-specific cellular immune response was induced at a significant level. No pathological symptom by vaccination was observed. After vaccination, exposure of simian immunodeficiency virus was performed and the effect was examined. As a result, the amount of virus in plasma significantly decreased, compared with that of the control animal. The present invention provides a promising vaccine as an AIDS vaccine.

    摘要翻译： 本发明提供含有编码免疫缺陷病毒病毒蛋白质的仙台病毒载体的疫苗。 通过将编码免疫缺陷病毒的病毒蛋白的仙台病毒鼻内施用于猕猴，本发明人成功地有效地诱导针对免疫缺陷病毒的保护性免疫。 鼻内接种疫苗后，在鼻内粘膜中检测到仙台病毒载体介导的抗原蛋白的表达，局部淋巴结的表达明显升高，抗原特异性细胞免疫应答水平明显升高。 未观察到接种疫苗的病理症状。 接种疫苗后，进行猿猴免疫缺陷病毒的暴露，并检查其效果。 结果，与对照动物相比，血浆中的病毒量显着降低。 本发明提供了作为AIDS疫苗的有希望的疫苗。

    AIDS VIRUS VACCINES USING SENDAI VIRUS VECTOR
    8.
    发明申请
    AIDS VIRUS VACCINES USING SENDAI VIRUS VECTOR 有权
    艾滋病病毒疫苗使用SENDAI病毒载体

    公开(公告)号：US20100266633A1

    公开(公告)日：2010-10-21

    申请号：US12701303

    申请日：2010-02-05

    申请人： Munehide KANO ,  Tetsuro Matano ,  Atsushi Kato ,  Yoshiyuki Nagai ,  Mamoru Hasegawa

    发明人： Munehide KANO ,  Tetsuro Matano ,  Atsushi Kato ,  Yoshiyuki Nagai ,  Mamoru Hasegawa

    IPC分类号： A61K39/21

    CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/53 ,  A61K2039/543 ,  A61K2039/545 ,  A61K2039/57 ,  C12N2740/15034 ,  C12N2760/18843 ,  C12N2760/18871 ,  C12N2800/30

    摘要： The present invention provides a vaccine containing a Sendai virus vector encoding a virus protein of an immunodeficiency virus. By intranasally administering a Sendai virus encoding a virus protein of an immunodeficiency virus to a macaque monkey, the present inventors have succeeded in efficiently inducing protective immunity against an immunodeficiency virus. As a result of intranasal inoculation of vaccine, expression of an antigen protein mediated by Sendai virus vector was detected in intranasal mucous membrane and local lymph nodes and antigen-specific cellular immune response was induced at a significant level. No pathological symptom by vaccination was observed. After vaccination, exposure of simian immunodeficiency virus was performed and the effect was examined. As a result, the amount of virus in plasma significantly decreased, compared with that of the control animal. The present invention provides a promising vaccine as an AIDS vaccine.

    摘要翻译： 本发明提供含有编码免疫缺陷病毒病毒蛋白质的仙台病毒载体的疫苗。 通过将编码免疫缺陷病毒的病毒蛋白的仙台病毒鼻内施用于猕猴，本发明人成功地有效地诱导针对免疫缺陷病毒的保护性免疫。 鼻内接种疫苗后，在鼻内粘膜中检测到仙台病毒载体介导的抗原蛋白的表达，局部淋巴结的表达明显升高，抗原特异性细胞免疫应答水平明显升高。 未观察到接种疫苗的病理症状。 接种疫苗后，进行猿猴免疫缺陷病毒的暴露，并检查其效果。 结果，与对照动物相比，血浆中的病毒量显着降低。 本发明提供了作为AIDS疫苗的有希望的疫苗。

    Paramyxovirus vectors used for transfer of foreign genes
    10.
    发明授权
    Paramyxovirus vectors used for transfer of foreign genes 失效
    用于转移外来基因的副粘病毒载体

    公开(公告)号：US06746860B1

    公开(公告)日：2004-06-08

    申请号：US09702498

    申请日：2000-10-31

    申请人： Tsuyoshi Tokusumi ,  Akihiro Iida ,  Mamoru Hasegawa ,  Yoshiyuki Nagai

    发明人： Tsuyoshi Tokusumi ,  Akihiro Iida ,  Mamoru Hasegawa ,  Yoshiyuki Nagai

    IPC分类号： C12N701

    CPC分类号： C12N15/86 ,  C12N2760/18843 ,  C12N2830/42

    摘要： A paramyxovirus vector capable of Extransfecting foreign genes and having a replication capacity, is provided. A Sendai virus vector comprising a foreign gene can be constructed by inserting a foreign gene between the viral genes of the Sendai virus genome. These Sendai viruses have a replication capacity and express the foreign gene in transfected cells. The expression level of the foreign gene is higher towards the 3′ end of negative strand RNA, and especially, a high level of expression is obtained when the foreign gene is inserted before the NP gene, and between P gene and M gene. Conversely, the expression decreases towards 5′ end of negative strand RNA, and especially, a relatively low level of expression is obtained when the when the foreign gene is inserted between HN gene and L gene, and between F gene and HN gene. Thus, the vector of the invention enables the regulation of the expression level of a foreign gene. The vector is useful for gene therapy due to its safety, high gene transfer efficiency, and capacity to express a foreign gene at a high level.

    摘要翻译： 提供了能够外切基因并具有复制能力的副粘病毒载体。 可以通过在仙台病毒基因组的病毒基因之间插入外来基因来构建包含外来基因的仙台病毒载体。 这些仙台病毒具有复制能力，并在转染的细胞中表达外源基因。 外源基因的表达水平高于负链RNA的3'末端，特别是当外源基因插入NP基因之前和P基因与M基因之间时，可获得高水平的表达。 相反，表达量向负链RNA的5'端减少，特别是当外源基因插入到HN基因和L基因之间以及F基因和HN基因之间时，获得相对低的表达水平。 因此，本发明的载体能够调节外源基因的表达水平。 该载体由于其安全性，高基因转移效率和在高水平表达外源基因的能力而可用于基因治疗。