Adenovirus vectors lacking virus-associated RNA expression enhance shRNA activity to suppress hepatitis C virus replication.
Adenovirus vectors lacking virus-associated RNA expression enhance shRNA activity to suppress hepatitis C virus replication.
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DOI：
10.1038/srep03575
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发表时间：
2013-12-20
影响因子：
4.6
通讯作者：
Kanegae, Yumi
中科院分区：
文献类型：
--
作者：
Pei, Zheng;Shi, Guoli;Kondo, Saki;Ito, Masahiko;Maekawa, Aya;Suzuki, Mariko;Saito, Izumu;Suzuki, Tetsuro;Kanegae, Yumi
第一代腺病毒载体（FG AdVs）表达短发夹RNA（shRNA）有效地下调靶基因的表达。然而，事实上，该载体不仅表达转基因产物，还表达干扰细胞RNAi机制的病毒相关RNA（VA RNA）。我们已经建立了一种生产VA缺失的AdV的方法，缺乏VA RNA的表达。在这里，我们表明，当shRNA不是插入在常用的E1位点，而是插入在E4位点时，获得了最高的shRNA活性。然后我们比较了从VA缺失的AdV或常规AdV表达的针对丙型肝炎病毒（HCV）的shRNA的活性。VA缺失的AdV更有效地抑制HCV的产生。因此，VA缺失的AdV比目前使用的AdV更有效地下调shRNA，可能是因为VA RNA和shRNA之间缺乏竞争。这些VA缺失的AdV可能使慢性丙型肝炎的基因治疗更有效。
First-generation adenovirus vectors (FG AdVs) expressing short-hairpin RNA (shRNA) effectively downregulate the expressions of target genes. However, this vector, in fact, expresses not only the transgene product, but also virus-associated RNAs (VA RNAs) that disturb cellular RNAi machinery. We have established a production method for VA-deleted AdVs lacking expression of VA RNAs. Here, we showed that the highest shRNA activity was obtained when the shRNA was inserted not at the popularly used E1 site, but at the E4 site. We then compared the activities of shRNAs against hepatitis C virus (HCV) expressed from VA-deleted AdVs or conventional AdVs. The VA-deleted AdVs inhibited HCV production much more efficiently. Therefore, VA-deleted AdVs were more effective than the currently used AdVs for shRNA downregulation, probably because of the lack of competition between VA RNAs and the shRNAs. These VA-deleted AdVs might enable more effective gene therapies for chronic hepatitis C.
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DOI：
10.1111/j.1440-1746.2007.05076.x
发表时间：
2008-09-01
影响因子：
4.1
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
3.8
作者：
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NAIRN, R
影响因子：
5.4
作者：
Lu, SH;Cullen, BR
通讯作者：
Cullen, BR
DOI：
10.1073/pnas.1009823107
发表时间：
2010-10-05
影响因子：
11.1
作者：
Yamaguchi, Tomoko;Kawabata, Kenji;Mizuguchi, Hiroyuki
通讯作者：
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