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    RECOMBINANT PARAINFLUENZA VIRUS VACCINES ATTENUATED BY DELETION OR ABLATION OF THE C, D OR V GENES
    87.
    发明申请
    RECOMBINANT PARAINFLUENZA VIRUS VACCINES ATTENUATED BY DELETION OR ABLATION OF THE C, D OR V GENES 审中-公开
    通过C，D或V基因的删除或消除而破坏的重组腺病毒病毒疫苗

    公开(公告)号：WO0103744A3

    公开(公告)日：2001-09-13

    申请号：PCT/US0018523

    申请日：2000-07-06

    Applicant: US GOV HEALTH & HUMAN SERV ,  DURBIN ANNA P ,  COLLINS PETER L ,  MURPHY BRIAN R

    Inventor： DURBIN ANNA P ,  COLLINS PETER L ,  MURPHY BRIAN R

    IPC: C12N15/09 ,  A61K9/12 ,  A61K39/00 ,  A61K39/102 ,  A61K48/00 ,  A61P31/16 ,  C07K14/115 ,  C12N7/00 ,  C12N7/04 ,  C12N15/45 ,  A61K39/155 ,  C12N15/11

    CPC classification number: C12N7/00 ,  A61K39/00 ,  A61K2039/522 ,  C07K14/005 ,  C12N2760/18622 ,  C12N2760/18643 ,  C12N2760/18661

    Abstract: Recombinant parainfluenza virus (PIV) are provided in which expression of the C, D and/or V translational open reading frame(s) (ORFs) is reduced or ablated to yield novel PIV vaccine candidates. Expression of the C, D and/or V ORF(s) is reduced or ablated by modifying a recombinant PIV genome or antigenome, for example by introduction of a stop codon, by a mutation in an RNA editing site, by a mutation that alters the amino acid specified by an initiation codon, or by a frame shift mutation in the targeted ORF(s). Alternatively, the C, D and/or V ORF(s) is deleted in whole or in part to render the protein(s) encoded thereby partially or entirely non-functional or to disrupt protein expression altogether. C, D and/or V ORF(s) deletion and knock out mutants possess highly desirable phenotypic characteristics for vaccine development. These deletion and knock out mutations changes specify one or more desired phenotypic changes in the resulting virus or subviral particle. Vaccine candidates are generated that show a change in viral growth characteristics, attenuation, plaque size, and/or a change in cytopathogenicity, among other novel phenotypes. A variety of additional mutations and nucleotide modifications are provided within the C, D and/or V ORF(s) deletion or ablation mutant PIV of the invention to yield desired phenotypic and structural effects.

    Abstract translation: 提供了重组副流感病毒（PIV），其中C，D和/或V翻译开放阅读框（ORF）的表达被降低或消融以产生新型PIV疫苗候选物。 C，D和/或V ORF的表达通过修饰重组PIV基因组或反义基因组，例如通过引入终止密码子，通过RNA编辑位点中的突变，通过改变的突变来降低或消除 由起始密码子指定的氨基酸或靶向ORF中的帧位移突变。 或者，C，D和/或V ORF全部或部分缺失，以使由此编码的蛋白质部分或完全不起作用或完全破坏蛋白质表达。 C，D和/或V ORF（s）缺失和敲除突变体对疫苗开发具有非常需要的表型特征。 这些缺失和敲除突变变化指定了所得病毒或亚病毒颗粒中的一种或多种期望的表型变化。 产生疫苗候选物，其显示病毒生长特征，衰减，斑块大小和/或细胞致病性变化以及其他新型表型之间的变化。 本发明的C，D和/或V ORF缺失或消融突变体PIV中提供了多种其它突变和核苷酸修饰，以产生所需的表型和结构效果。

    USE OF PARAMYXOVIRUS VECTOR IN GENE TRANSFER INTO BLOOD VESSEL
    88.
    发明申请
    USE OF PARAMYXOVIRUS VECTOR IN GENE TRANSFER INTO BLOOD VESSEL 审中-公开
    将遗传病毒载体转入血液中的使用

    公开(公告)号：WO01053491A1

    公开(公告)日：2001-07-26

    申请号：PCT/JP2001/000087

    申请日：2001-01-11

    IPC: A61K48/00 ,  C12N15/45 ,  C12N15/86 ,  C12Q1/68

    CPC classification number: C12N15/86 ,  A61K48/00 ,  A61K48/0008 ,  C12N2760/18843 ,  C12N2800/30

    Abstract: Use of a paramyxovirus vector makes it possible to transfer a nucleic acid into a blood vessel at a high efficiency even by exposing to the vector within a short period of time. Namely, a paramyxovirus vector to be used for transferring a nucleic acid into vascular cells and a nucleic acid transfer method with the use of this virus vector are provided. The gene transfer efficiency into the vascular media layer is significantly elevated by treating the blood vessel with a protease. The expression of the transferred gene remains stable over a long time in the vascular cells. Use of this method makes it possible to efficiently transfer a gene within a short period of time into the vascular cavity, media, tunica tissues, etc. in gene therapy.

    Abstract translation: 使用副粘病毒载体使得可以在短时间内将核酸以高效率转移到血管中，甚至通过暴露于载体。 即，提供将用于将核酸转移到血管细胞中的副粘病毒载体和使用该病毒载体的核酸转移方法。 通过用蛋白酶处理血管，进入血管介质层的基因转移效率显着升高。 所转移的基因的表达在血管细胞中长时间保持稳定。 使用该方法可以在短时间内将基因有效地转移到基因治疗中的血管腔，培养基，中膜组织等中。

    PARAMYXOVIRUSES HAVING MODIFIED TRANSCRIPTION INITIATION SEQUENCE
    90.
    发明申请
    PARAMYXOVIRUSES HAVING MODIFIED TRANSCRIPTION INITIATION SEQUENCE 审中-公开
    具有修饰转录启动序列的参与药物

    公开(公告)号：WO01018223A1

    公开(公告)日：2001-03-15

    申请号：PCT/JP2000/006051

    申请日：2000-09-06

    IPC: A61K48/00 ,  C07K14/115 ,  C12N15/45 ,  C12N15/86

    CPC classification number: C07K14/005 ,  A61K48/00 ,  C12N15/86 ,  C12N2760/18822 ,  C12N2760/18843

    Abstract: Virus vectors of the family Paramyxoviridae in which the transcription initiation sequence has been modified and thus the expression of genes located downstream thereof has been modified; a process for producing the same; and use of the same. By measuring the transcription initiation efficiency of each gene carried by Sendai viruses, it is clarified that the transcription initiation sequence of F gene has a significantly lower ability to promote the transcription than the three other transcription initiation sequences. When the transcription initiation sequence of the F gene of wild type Sendai virus is substituted by the transcription initiation sequence of the P/M/HN genotype showing a high efficiency, the F gene of the resultant Sendai virus mutant and genes located downstream thereof show elevated expression doses. It is also found out that this mutant proliferates more quickly than the wild type. The above-described vectors are useful in producing medicinal compositions and vaccines.

    Abstract translation: 其中转录起始序列已被修饰并因此位于其下游的基因的表达已被修饰的副粘病毒科的病毒载体< 其制造方法; 并使用相同的。 通过测量仙台病毒携带的每种基因的转录起始效率，阐明了F基因的转录起始序列与其他三种转录起始序列相比，具有显着较低的促进转录能力。 当野生型仙台病毒的F基因的转录起始序列被P / M / HN基因型的转录起始序列代替时，产生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 表达剂量。 还发现该突变体比野生型增殖更快。 上述载体可用于生产药物组合物和疫苗。

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