Chimeric adenoviral vectors incorporating a fiber of human adenovirus 3 efficiently mediate gene transfer into prostate cancer cells.
Chimeric adenoviral vectors incorporating a fiber of human adenovirus 3 efficiently mediate gene transfer into prostate cancer cells.
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DOI：
10.1002/pros.21070
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发表时间：
2010-03-01
期刊：
影响因子：
2.8
通讯作者：
Curiel, David T.
中科院分区：
文献类型：
--
作者：
Murakami, Miho;Ugai, Hideyo;Belousova, Natalya;Pereboev, Alexander;Dent, Paul;Fisher, Paul B.;Everts, Maaike;Curiel, David T.
我们已经开发了一系列基于人腺病毒血清5型(HAdV-5)的腺病毒(AdV-5)载体，展示了B种病毒(HAdV-3、HAdV-11或HAdV-35)的纤维轴和节区。这些B类ADS利用与HAdV-5不同的细胞受体进行感染。我们评估了显示B种纤维轴和节结构域的Ad载体(Ad5F3Luc1、Ad5F11Luc1和Ad5F35Luc1)是否能有效地感染包括前列腺癌在内的不同来源的癌细胞。以荧光素酶为报告基因，将构建的纤维嵌合Ad载体与原始Ad载体(Ad5Luc1)在多种癌细胞系中的转导效率进行比较，包括前列腺癌和原代前列腺上皮细胞(PREC)。感染Ad5F3Luc1的前列腺癌细胞株的荧光素酶表达水平高于Ad5Luc1和其他嵌合Ad载体。我们还通过监测前列腺癌细胞中荧光素酶的活性来分析其转导效率，这些荧光素酶在前前列腺癌细胞中作为基因转移的一部分表达。在PC-3和DU145细胞系中，Ad5F3Luc1对癌细胞和前癌基因的转移率再次最高。在所研究的嵌合HAdV-5/物种B载体中，Ad5F3Luc1被认为是最适合靶向前列腺癌细胞的载体，因为它在这些细胞中具有最高的转导效率。可以预见的是，含有HAdV-3纤维的Ad载体有可能用于前列腺癌的基因治疗。
We have developed a range of adenoviral (Ad) vectors based on human adenovirus serotype 5 (HAdV-5) displaying the fiber shaft and knob domains of species B viruses (HAdV-3, HAdV-11, or HAdV-35). These species B Ads utilize different cellular receptors than HAdV-5 for infection. We evaluated whether Ad vectors displaying species B fiber shaft and knob domains (Ad5F3Luc1, Ad5F11Luc1, and Ad5F35Luc1) would efficiently infect cancer cells of distinct origins, including prostate cancer. The fiber chimeric Ad vectors were genetically generated and compared with the original Ad vector (Ad5Luc1) for transductional efficiency in a variety of cancer cell lines, including prostate cancer cells and primary prostate epithelial cells (PrEC), using luciferase as a reporter gene. Prostate cancer cell lines infected with Ad5F3Luc1 expressed higher levels of luciferase than Ad5Luc1, as well as the other chimeric Ad vectors. We also analyzed the transductional efficiency via monitoring of luciferase activity in prostate cancer cells when expressed as a fraction of the gene transfer in PrEC cells. In the PC-3 and DU145 cell lines, the gene transfer ratio of cancer cells versus PrEC was once again highest for Ad5F3Luc1. Of the investigated chimeric HAdV-5/species B vectors, Ad5F3Luc1 was judged to be the most suitable for targeting prostate cancer cells as it showed the highest transductional efficiency in these cells. It is foreseeable that an Ad vector incorporating the HAdV-3 fiber could potentially be used for prostate cancer gene therapy.
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影响因子：
12.3
作者：
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影响因子：
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作者：
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