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短发夹RNA表达载体在核心蛋白表达型Huh-7细胞中对丙型肝炎病毒核心蛋白的抑制作用

Suppression of hepatitis C virus core protein by short hairpin RNA expression vectors in the core protein expression Huh-7 cells.

作者信息

Suzuki Hitoshi, Kaneko Hiroyasu, Tamai Nobushige, Shimotohno Kunitada, Miyano-Kurosaki Naoko, Takaku Hiroshi

机构信息

Department of Life and Environmental Sciences, Chiba Institute of Technology, Chiba, Japan.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2007;26(6-7):815-20. doi: 10.1080/15257770701503787.

DOI:10.1080/15257770701503787
PMID:18066906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2403745/
Abstract

Short hairpin RNAs (shRNAs) efficiently inhibit gene expression by RNA interference. Here, we report the efficient inhibition by DNA-based vector-derived shRNAs of core protein expression in Huh-7 cells. The shRNAs were designed to target the core region of the hepatitis C virus (HCV) genome. The core region is the most conserved region in the HCV genome, making it an ideal target for shRNAs. We identified an effective site on the core region for suppression of the HCV core protein. The HCV core protein in core protein-expressing Huh-7 cells was downregulated by core protein-shRNA expression vectors (core-shRNA-452, 479, and 503). Our results support the feasibility of using shRNA-based gene therapy to inhibit HCV core protein production.

摘要

短发夹RNA(shRNA)通过RNA干扰有效抑制基因表达。在此,我们报道了基于DNA载体的shRNA对Huh-7细胞中核心蛋白表达的有效抑制。这些shRNA被设计用于靶向丙型肝炎病毒(HCV)基因组的核心区域。核心区域是HCV基因组中最保守的区域,使其成为shRNA的理想靶点。我们在核心区域鉴定出一个用于抑制HCV核心蛋白的有效位点。表达核心蛋白的Huh-7细胞中的HCV核心蛋白被核心蛋白-shRNA表达载体(核心-shRNA-452、479和503)下调。我们的结果支持使用基于shRNA的基因疗法抑制HCV核心蛋白产生的可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/2403745/3fcae6d647e5/lncn26-815-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/2403745/41931a646ac8/lncn26-815-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/2403745/0fa717b1b871/lncn26-815-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/2403745/3fcae6d647e5/lncn26-815-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/2403745/41931a646ac8/lncn26-815-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/2403745/0fa717b1b871/lncn26-815-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/2403745/3fcae6d647e5/lncn26-815-f3.jpg

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本文引用的文献

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J Virol. 2003 Oct;77(19):10237-49. doi: 10.1128/jvi.77.19.10237-10249.2003.
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Inhibition of intracellular hepatitis C virus replication by synthetic and vector-derived small interfering RNAs.合成的和载体衍生的小干扰RNA对细胞内丙型肝炎病毒复制的抑制作用。
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Gene silencing by systemic delivery of synthetic siRNAs in adult mice.
成年小鼠中通过合成小干扰RNA的全身递送实现基因沉默。
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RNA interference blocks gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells.RNA干扰可阻断在人肝细胞中增殖的丙型肝炎复制子的基因表达和RNA合成。
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2783-8. doi: 10.1073/pnas.252758799. Epub 2003 Feb 19.
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Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs.利用小干扰RNA在细胞培养中清除复制的丙型肝炎病毒复制子RNA
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