首页> 外国专利> RECOMBINANT ADENOVIRUS COMPRISING HTERT MRNA TARGETING RIBOZYME AND P53 GENE

RECOMBINANT ADENOVIRUS COMPRISING HTERT MRNA TARGETING RIBOZYME AND P53 GENE

机译:重组腺病毒,包含靶向mRNA的核糖核酸酶和P53基因

摘要

The present invention relates to: a recombinant adenovirus; a host cell into which the recombinant adenovirus is introduced; a pharmaceutical composition comprising the recombinant adenovirus as an active ingredient for preventing or treating cancers; and a method for treating cancers comprising the step of administering the pharmaceutical composition including the recombinant adenovirus as an active ingredient to a subject in need of treatment at a pharmaceutically effective amount, wherein, the recombinant adenovirus comprises a promoter, a ribozyme which is targeted to human telomerase reverse transcriptase (hTERT) mRNA, and a p53 gene in an adenovirus backbone of which E1 and E3 are deleted. The recombinant adenovirus of the present invention inhibits the activity of hTERT mRNA, which is specifically overexpressed in cancer cells, by cutting hTERT mRNA through a trans-splicing ribozyme, and simultaneously allows p53, which is a therapeutic gene, to be expressed. Thus it is confirmed that cancer cells are effectively killed using the recombinant adenovirus of the present invention. Particularly, it is confirmed that liver tissue-specific migration, particularly selective motility toward cancer cells, is improved. Thus, since the recombinant adenovirus of the present invention does not show cell cytotoxicity to normal cells for systemic administration by having improved selective motility, the present invention can be used as a gene therapeutic agent for hepatoma cancer or metastatic liver cancer.
机译:本发明涉及:重组腺病毒;导入了重组腺病毒的宿主细胞;包含重组腺病毒作为预防或治疗癌症的活性成分的药物组合物;以及治疗癌症的方法,其包括以下步骤:以药物有效量向需要治疗的受试者施用包含重组腺病毒作为活性成分的药物组合物,其中,所述重组腺病毒包含启动子,靶向核酶的核酶。人端粒酶逆转录酶(hTERT)mRNA和缺失E1和E3的腺病毒骨架中的p53基因。本发明的重组腺病毒通过通过转拼核酶切割hTERT mRNA来抑制在癌细胞中特异性过表达的hTERT mRNA的活性,并同时表达治疗基因p53。因此证实了使用本发明的重组腺病毒可有效杀死癌细胞。特别地,已证实改善了肝组织特异性迁移,特别是向癌细胞的选择性运动。因此,由于本发明的重组腺病毒不具有通过改善的选择性运动而对用于全身给药的正常细胞的细胞毒性,因此本发明可以用作肝癌或转移性肝癌的基因治疗剂。

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