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    Mutant TAR virus and transdominant tat mutants as pharmacological agents
    3.
    发明授权
    Mutant TAR virus and transdominant tat mutants as pharmacological agents 失效
    突变型TAR病毒和转核突变体作为药理作用

    公开(公告)号：US5994108A

    公开(公告)日：1999-11-30

    申请号：US286874

    申请日：1994-08-05

    申请人： Richard B. Gaynor ,  David Harrich

    发明人： Richard B. Gaynor ,  David Harrich

    IPC分类号： A61K38/00 ,  A61K39/00 ,  C07K14/16 ,  C12N15/48 ,  C12N5/10 ,  C12N7/01 ,  C12N15/10

    CPC分类号： C07K14/005 ,  A61K38/00 ,  A61K39/00 ,  C12N2740/16322

    摘要： Transdominant HIV tat substitution and truncated gene mutants of 72 amino acid residues or less are disclosed. The mutated genes encode mutant Tat proteins which are capable of inhibiting the expression of the HIV-1 virus in the presence of an equimolar concentration of the wild type Tat protein in vitro. Therapeutic agents which include fused protein forms of the mutant proteins are also disclosed, as well as methods of preparing and using the therapeutic agents in the treatment of HIV infection and HIV-related injections in an animal. Recombinant vectors which express the mutant HIV Tat proteins described are also disclosed, as well as cell lines which product high yields of the mutant HIV. Also provided are cell lines that express enhanced levels of TAR mutant viruses relative to other TAR mutant infected cell lines. Levels of production are enhanced by the use of cell lines that express a transactivator protein, such as adenovirus transactivator EIA and/or EIB protein. Methods of preparing these cell lines, as well as vaccines from virus produced by these cell lines, are also disclosed.

    摘要翻译： 公开了72个氨基酸残基或以下的显性HIV tat取代和截短基因突变体。 突变的基因编码突变的Tat蛋白，其能够在体外在等摩尔浓度的野生型Tat蛋白存在下抑制HIV-1病毒的表达。 还公开了包括突变蛋白质的融合蛋白形式的治疗剂，以及制备和使用治疗剂在动物中治疗HIV感染和HIV相关注射的方法。 还公开了表达所描述的突变型HIV Tat蛋白的重组载体，以及产生突变型HIV高产量的细胞系。 还提供了相对于其他TAR突变体感染的细胞系表达增强水平的TAR突变病毒的细胞系。 通过使用表达反式激活蛋白的细胞系，例如腺病毒反式激活剂EIA和/或EIB蛋白来增强生产水平。 还公开了制备这些细胞系的方法以及由这些细胞系产生的病毒的疫苗。