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    Self-regulated apoptosis of inflammatory cells
    1.
    发明授权
    Self-regulated apoptosis of inflammatory cells 失效
    自身调节凋亡细胞炎症细胞

    公开(公告)号：US06525184B1

    公开(公告)日：2003-02-25

    申请号：US09032297

    申请日：1998-02-27

    Applicant: Revati J. Tatake ,  Steven D. Marlin ,  Randall W. Barton

    Inventor： Revati J. Tatake ,  Steven D. Marlin ,  Randall W. Barton

    IPC: C07H2104

    CPC classification number: C12N9/6475 ,  A61K38/00 ,  A61K48/00 ,  C07K14/4747 ,  C07K14/525 ,  C07K2319/00 ,  C12N15/85 ,  C12N2830/001 ,  C12N2830/002 ,  C12N2830/15 ,  C12N2830/30

    Abstract: This invention relates to the therapeutic induction of apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells a chimeric gene containing an apoptosis-inducing gene (AIG) driven by a promoter of an inducible gene activated in inflammation and a promoter enhancer such that the inflammatory cells are targeted. In one embodiment, the chimeric gene comprises at least one TNF&agr; promoter enhancer attached to a functional copy of a minimal TNF&agr; promoter and further attached to at least one copy of an apoptosis-inducing gene, wherein expression of the gene is driven by the TNF&agr; promoter. Attachment can be direct, distal, proximal or combinations thereof. Example apoptosis-inducing genes include caspase 3, caspase 4, caspase 5, Granzyme B. Advantageously, the TNFp-AIG chimeric gene is expressed in only those cells producing the inflammatory cytokine, TNF&agr;. In addition, the TNFp-AIG chimeric gene also sequesters inducible TNFp transcription factors, thereby reducing endogenous production of TNF&agr;. The invention also relates to methods of making and using self-regulated apoptosis chimeric genes and pharmaceutical compositions containing them for treating inflammatory diseases.

    Abstract translation: 本发明涉及在活化的炎性细胞或炎症部位的细胞中的细胞凋亡的治疗诱导，通过将包含由炎性激活的诱导型基因的启动子驱动的凋亡诱导基因（AIG）的嵌合基因导入那些细胞 和启动子增强子，使得炎症细胞被靶向。 在一个实施方案中，嵌合基因包含至少一个与最小TNFα启动子的功能拷贝连接的TNFα启动子增强子，并进一步连接至凋亡诱导基因的至少一个拷贝，其中该基因的表达由TNFα启动子 。 附件可以是直接的，远端的，近端的或其组合。 实例细胞凋亡诱导基因包括半胱天冬酶3，半胱天冬酶4，半胱天冬酶5，粒酶B.有利地，TNFp-AIG嵌合基因仅在产生炎性细胞因子TNFα的那些细胞中表达。 此外，TNFp-AIG嵌合基因还螯合诱导型TNFp转录因子，从而减少TNFalpha的内源性产生。 本发明还涉及制备和使用自我调节的凋亡嵌合基因的方法以及含有它们用于治疗炎性疾病的药物组合物。

    Self-regulated apoptosis of inflammatory cells by gene therapy
    5.
    发明授权
    Self-regulated apoptosis of inflammatory cells by gene therapy 有权
    通过基因治疗自发调节炎症细胞凋亡

    公开(公告)号：US06537784B1

    公开(公告)日：2003-03-25

    申请号：US09229151

    申请日：1999-01-12

    Applicant: Revati J. Tatake ,  Steven D. Marlin ,  Randall W. Barton

    Inventor： Revati J. Tatake ,  Steven D. Marlin ,  Randall W. Barton

    IPC: C12P1934

    CPC classification number: C12N9/6467 ,  A61K38/00 ,  A61K48/00 ,  C07K14/525 ,  C12N15/85 ,  C12N2830/00 ,  C12N2830/002 ,  C12N2830/15 ,  C12N2830/85

    Abstract: This invention relates to chimeric nucleic acids and to the therapeutic induction of apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells the chimeric nucleic acid. The chimeric nucleic acid having at least one TNF&agr; promoter enhancer attached to a functional copy of a TNF&agr; promoter and further attached to at least one copy of an apoptosis-inducing gene, which is further attached to a 3′UTR. The apoptosis-inducing gene is Granzyme B. The invention also relates to methods of making and using self-regulated apoptosis chimeric nucleic acids and pharmaceutical compositions containing them for treating inflammatory diseases.

    Abstract translation: 本发明涉及嵌合核酸和通过将嵌合核酸引入那些细胞中的活化炎症细胞或炎症部位的细胞的细胞凋亡的治疗诱导。 具有至少一个TNFalpha启动子增强子的嵌合核酸与TNFalpha启动子的功能拷贝连接，并进一步连接至凋亡诱导基因的至少一个拷贝，其进一步连接到3'UTR。 凋亡诱导基因是颗粒酶B.本发明还涉及制备和使用自我调节的凋亡嵌合核酸的方法和含有它们的药物组合物用于治疗炎症性疾病。

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