Recombinant Sendai viruses expressing different levels of a foreign reporter gene

Recombinant Sendai viruses expressing different levels of a foreign reporter gene
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DOI:
10.1016/s0168-1702(02)00047-3
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发表时间:
2002-06-01
期刊:
影响因子:
5
通讯作者:
Hasegawa, M
Hasegawa, M
中科院分区:
医学3区
文献类型:
--
作者:
Tokusumi, T;Iida, A;Hasegawa, M

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仙台病毒 (SeV) 是一种有包膜病毒,具有不分段的负链 RNA 基因组。已证明从 cDNA 中回收感染性病毒并产生在启动子近端位置携带外源基因的重组 SeV。在本研究中,我们构建了一系列重组SeV,在每个病毒基因连接处或5'远端携带报告人分泌碱性磷酸酶(SEAP)基因,以测量外源基因的表达水平。我们证明,由于转录的极性,报告基因表达水平存在依赖于位置的梯度。相反,这些重组病毒的生长和最终滴度表现出与外源基因表达水平相反的梯度。这表明当 SeV 用作人类基因治疗的载体时,通过改变外源基因的位置,有可能将治疗基因表达水平与个体治疗方案相匹配。 (C) 2002 爱思唯尔科学 B,V。版权所有。
Sendai virus (SeV) is an enveloped virus with a nonsegmented negative strand RNA genome. The recovery of infectious virus from cDNA and generation of recombinant SeV carrying a foreign gene at the promoter proximal position has been demonstrated. In this study, we constructed a series of recombinant SeVs carrying a reporter human secreted alkaline phosphatase (SEAP) gene at each viral gene junction or the 5' distal end in order to measure the expression level of the foreign gene. We demonstrated that there was a gradient in the reporter gene expression level that depended on location, due to the polarity of transcription. In contrast, the growth and final titers of these recombinant viruses showed an opposite gradient to the foreign gene expression level. This suggests the potential for matching therapeutic gene expression level to individual therapy programs by changing the position of the foreign gene when SeVs are used as vectors for human gene therapy. (C) 2002 Elsevier Science B,V. All rights reserved.