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Gene therapy vectors harboring AFP regulatory sequences

机译：带有AFP调控序列的基因治疗载体

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Gene therapy for hepatocellular carcinoma (HCC) may be acieved by introducing a therapeutic gene under the control of transcriptional regulatory sequences of the #alpha#-fetoprotein (AFP) gene.Transcription of the human AFP gene is controlled positively by the promoter and the enhancer and negatively by the silencer.The AFP promoter is a 200-bp region immediately upstream of the AFP gene,and the enhancer is present between 3 and 4.9 kb upstream of the transcription initiation site.Two silencer regios have been identified upstream of the gene,one at-0.31 kb and the other at -1.75kb.To acieve specific killing of HCC,adenoviral vectors carrying AFP regulatory sequences have been contstructed.In this article,we describe the details of the preparation of an adenoviral vector designed to express the herpes simpelx virus thymidine kinase geneunder the control of the 4.9-kb AFP 5'-regulatory sequence.Treatment with this viral vector followed by ganciclovir resulted in specific killing of AFP-positive HCC transplanted in nude mice.Other viral vectors containing AFP-regualtory sequences are also discussed.
机译：肝细胞癌（HCC）的基因治疗可以通过在＃alpha＃甲胎蛋白（AFP）基因的转录调控序列的控制下引入治疗基因来实现.AFP基因的转录受启动子和增强子的正调控AFP启动子是AFP基因上游200 bp的区域，增强子位于转录起始位点上游3到4.9 kb之间。在该基因的上游发现了两个沉默子区域，一个在-0.31 kb处，另一个在-1.75kb处。为了特异性地杀死HCC，已经构建了带有AFP调控序列的腺病毒载体。在4.9-kb AFP 5'-调控序列的控制下，simpelx病毒胸苷激酶基因被该病毒载体治疗，随后更昔洛韦治疗导致AFP-p的特异性杀伤阳性的HCC移植到裸鼠体内。还讨论了其他含有AFP调控序列的病毒载体。

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