Adenovirus/alphavirus hybrid vector for the effective administration and expression of therapeutic genes in tumour cells
    1.
    发明授权
    Adenovirus/alphavirus hybrid vector for the effective administration and expression of therapeutic genes in tumour cells 失效
    用于在肿瘤细胞中有效施用和表达治疗基因的腺病毒/甲病毒属杂交载体

    公开(公告)号:US07850957B2

    公开(公告)日:2010-12-14

    申请号:US11569303

    申请日:2005-05-18

    IPC分类号: A01N63/00 A61K39/12 C12N15/00

    摘要: The present invention relates to a genic expression adenoviral hybrid vector characterized in that it contains at least the following elements, oriented in the direction 5′ to 3′: i. a first chain of adenoviral origin comprising a first inverted terminal repeat (ITR) sequence and a signal sequence for packaging of the adenovirus; ii. a first non-encoding stuffer sequence; iii. a sequence corresponding to a tissue specific promoter; iv. a chain of cDNA derived from an alphavirus, the sequence of which is partly complementary to an alphaviral RNA sequence, comprising at least a sequence encoding for at least one exogenous gene of interest; v. a polyadenylation sequence; and vi. a second adenoviral inverted terminal repeat (ITR) sequence, it preferably relates to an adenoviral hybrid vector comprising as exogenous gene of interest the therapeutic gene of mammalian interleukin IL-12 and even more preferably human interleukin hIL-12; and to the use of the hybrid vector in a process for transferring genetic material to a cell, particularly a tumor cell that preferably expresses alpha-fetoprotein (AFP), and to its use for inducing an immune response against foreign antigens.

    摘要翻译: 本发明涉及一种基因表达腺病毒杂合载体,其特征在于其至少包含以5'至3'方向取向的以下元件:i。 包括第一反向末端重复序列(ITR)序列和用于包装腺病毒的信号序列的第一个腺病毒源, ii。 第一个非编码填充序列; iii。 对应于组织特异性启动子的序列; iv。 源自甲病毒病毒的cDNA链,其序列与甲病毒RNA序列部分互补,包含至少一个编码至少一种感兴趣的外源基因的序列; v。多腺苷酸化序列; 和vi。 第二种腺病毒反向末端重复(ITR)序列,优选涉及包含作为感兴趣的外源基因的哺乳动物白介素IL-12的治疗基因,甚至更优选人白细胞介素hIL-12的腺病毒杂交载体; 以及将遗传物质转移到细胞,特别是优选表达甲胎蛋白(AFP)的肿瘤细胞的方法中以及其用于诱导针对外来抗原的免疫应答的用途的用途。