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RECOMBINANT ADENOVIRUS COMPRISING RIBOZYME TARGETING MRNA ENCODING HTERT AND P53 GENE

机译:包含核糖核酸靶向HTERT和P53基因的核糖核酸的重组腺病毒

摘要

The present invention relates to: a recombinant adenovirus comprising a promoter, a ribozyme targeting human telomerase reverse transcriptase (hTERT) mRNA, and a p53 gene, in an adenovirus backbone with deletions of E1 and E3; a host cell into which the recombinant adenovirus is introduced; and a pharmaceutical composition comprising the the recombinant adenovirus as an active ingredient for preventing or treating cancers. It was confirmed that the recombinant adenovirus of the present invention was used to inhibit the activity of hTERT mRNA, which is specifically overexpressed in cancer cells, by cutting the hTERT mRNA through a trans-splicing ribozyme, and simultaneously to allow p53, which is a therapeutic gene, to be expressed, thereby effectively killing cancer cells. Particularly, it was confirmed that the liver tissue-specific migration, particularly selective motility toward cancer cells, was improved. Thus, the recombinant adenovirus of the present invention can be used as a gene therapeutic agent against hepatoma cancer or metastatic liver cancer, which does not show cytotoxicity to normal cells regardless of systemic administration thereof and which has improved selective motility. [Reference numerals] (AA) CMV promoter; (BB) Therapeutic gene; (CC) h TERT ribozyme; (DD) Ad frame (E1&E3); (EE) Ribozyme (+)
机译:本发明涉及一种重组腺病毒,其在具有E1和E3缺失的腺病毒骨架中包含启动子,靶向人端粒酶逆转录酶(hTERT)mRNA的核酶和p53基因。导入了重组腺病毒的宿主细胞;药物组合物,其包含重组腺病毒作为预防或治疗癌症的活性成分。证实了本发明的重组腺病毒被用于通过经由转拼核酶切割hTERT mRNA并同时允许p53(其为p53)来抑制在癌细胞中特异性过表达的hTERT mRNA的活性。待表达的治疗基因,从而有效杀死癌细胞。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,本发明的重组腺病毒可以用作抗肝癌或转移性肝癌的基因治疗剂,无论其全身给药,其对正常细胞均无细胞毒性,并且选择性运动性得到改善。 [参考数字](AA)CMV启动子; (BB)治疗基因; (CC)h TERT核酶; (DD)广告框架(E1&E3); (EE)核酶(+)

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