Mutant TAR virus and transdominant tat mutants as pharmacological agents
    133.
    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

    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。

    Nucleic acid constructs containing HIV genes with mutated
inhibitory/instability regions and methods of using same
    136.
    发明授权
    Nucleic acid constructs containing HIV genes with mutated inhibitory/instability regions and methods of using same 失效
    含有具有突变的抑制/不稳定区域的HIV基因的核酸构建体及其使用方法

    公开(公告)号:US5972596A

    公开(公告)日:1999-10-26

    申请号:US50478

    申请日:1994-01-26

    摘要: A method of locating an inhibitory/instability sequence or sequences within the coding region of an mRNA and modifying the gene encoding that mRNA to remove these inhibitory/instability sequences by making clustered nucleotide substitutions without altering the coding capacity of the gene is disclosed. Constructs containing these mutated genes and host cells containing these constructs are also disclosed. The method and constructs are exemplified by the mutation of a Human Immunodeficiency Virus-1 Rev-dependent gag gene to a Rev-independent gag gene. Constructs useful in locating inhibitory/instability sequences within either the coding region or the 3' untranslated region of an mRNA are also disclosed. The exemplified constructs of the invention may also be useful in HIV-1 immunotherapy and immunoprophylaxis.

    摘要翻译: 公开了一种定位mRNA编码区内的抑制/不稳定序列或序列的方法,并且通过进行聚类核苷酸取代而改变基因的编码能力,修饰编码该mRNA的基因以去除这些抑制/不稳定序列。 还公开了含有这些突变基因的构建体和含有这些构建体的宿主细胞。 该方法和构建体的例子是将人免疫缺陷病毒-1 Rev依赖性gag基因突变为Rev独立的gag基因。 还公开了可用于定位mRNA的编码区或3'非翻译区内的抑制/不稳定序列的构建体。 本发明的示例性构建体也可用于HIV-1免疫治疗和免疫预防。

    Prevention and treatment of retroviral disease

    公开(公告)号:US5928930A

    公开(公告)日:1999-07-27

    申请号:US464137

    申请日:1995-06-05

    摘要: The present invention provides a non-infectious immunotherapeutic containing retroviral particles devoid of outer envelope proteins or containing selected antigens isolated from a retrovirus. There is also provided a vaccine effective against HIV. In one aspect, the immunogen is useful for immunizing an individual previously infected by a retrovirus including HIV, so as to induce immunoprotective factors protective against progression of the infection. In another aspect, the vaccine is useful for vaccinating an individual not previously infected with HIV in order to prevent subsequently acquired infection. In another aspect, there is provided a method of rendering a viral immunogen non-infectious. The immunogen may also be used to produce antibodies for passive immunotherapy, alone or in conjunction with active immunotherapy, in individuals infected with a retrovirus, including HIV, preferably those individuals exhibiting low levels of antibodies to retroviral gene products other than the outer envelope.