首页> 外国专利> A GENE DELIVERING VECTOR COMPRISING THE GENE ENCODING SOLUBLE AND SECRETABLE HOMOTRIMER FORMING RECOMBINANT HUMAN TRAIL

A GENE DELIVERING VECTOR COMPRISING THE GENE ENCODING SOLUBLE AND SECRETABLE HOMOTRIMER FORMING RECOMBINANT HUMAN TRAIL

机译:包含编码可溶且安全的均聚物形成重组人类轨迹的基因的基因传递载体

摘要

A gene-delivering vector comprising a gene encoding a recombinant human TRAIL(TNF(tumor necrosis factor)-related apoptosis-inducing ligand) having ability of forming soluble and secretable homotrimer is provided to inhibit growth of cancer cells, induce apoptosis of cancer cells, and improve safety of use by eliminating infectious properties from the vector through removing E1 and E3 genes associated with adenovirus replication. A shuttle vector pAdloxTRAIL for producing replication-incompetent adenovirus comprises an expression cassette containing a secretion signal sequence of SEQ ID NO:3, a trimer-forming domain of SEQ ID NO:4 and TRAIL gene of SEQ ID NO:1, a human gene high expression promoter selected from CMV(cytomegalovirus), RSV(Rous sarcoma virus) and beta-actin and loxP gene, wherein E1 and E3 genes required for adenovirus replication are removed from the shuttle vector. A replication-incompetent adenovirus Ad-stTRAIL(KCCM 10743P) produces soluble and secretable homotrimer. An anticancer agent comprises the replication-incompetent adenovirus.
机译:提供了一种基因传递载体,其包含编码具有形成可溶性和可分泌同型三聚体能力的重组人TRAIL(TNF(肿瘤坏死因子)相关的凋亡诱导配体)的基因,以抑制癌细胞的生长,诱导癌细胞的凋亡,通过消除与腺病毒复制相关的E1和E3基因,从载体中消除传染性,从而提高使用安全性。用于产生不能复制的腺病毒的穿梭载体pAdloxTRAIL包括表达盒,该表达盒含有SEQ ID NO:3的分泌信号序列,SEQ ID NO:4的三聚体形成域和SEQ ID NO:1的TRAIL基因,人基因。选自CMV(巨细胞病毒),RSV(鲁氏肉瘤病毒)和β-肌动蛋白和loxP基因的高表达启动子,其中从穿梭载体中去除了腺病毒复制所需的E1和E3基因。无复制能力的腺病毒Ad-stTRAIL(KCCM 10743P)产生可溶性和可分泌的同源三聚体。抗癌剂包括无复制能力的腺病毒。

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