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However, the development of an effective system for <jats:italic>in vivo<\/jats:italic> delivery of small interfering RNA (siRNA) to target organ remains a formidable challenge. Here, we develop a unique nanoparticle platform (VE-DC) composed of \u03b1-tocopherol (vitamin E) and cholesterol-based cationic liposomes (DOTAP-Chol) for systemic delivery of siRNAs to the liver. A HCV-replicable cell line, Huh7.5.1-HCV and a transient HCV core expressing cell line, Huh7.5.1-Core, were constructed and used to assess the <jats:italic>in vitro<\/jats:italic> anti-HCV activity of VE-DC\/siRNAs. A transient <jats:italic>in vivo<\/jats:italic> HCV model was also constructed by hydrodynamic injection of pCDNA3.1(+)-3FLAG-Core (pCore-3FLAG) plasmid expressing core protein or pGL3-5\u2032UTR-luciferase (pGL3-5\u2032UTR-luc) plasmid expressing luciferase driven by HCV 5\u2032UTR. Nanoscale VE-DC\/siRNA was intravenously injected to assess the liver-targeting property as well as antiviral activity. The nanoscale VE-DC effectively exerted an anti-HCV activity in the <jats:italic>in vitro<\/jats:italic> cell models. Post-administration of VE-DC\/siRNAs also effectively delivered siRNAs to the liver, suppressing core protein production and firefly luciferase activity, without inducing an innate immunity response or off-target and toxicity effects. The VE-DC platform has high potential as a vehicle for delivery of siRNAs to the liver for gene therapy for targeting hepatitis C.<\/jats:p>","DOI":"10.1038\/srep24867","type":"journal-article","created":{"date-parts":[[2016,4,26]],"date-time":"2016-04-26T10:11:39Z","timestamp":1461665499000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Target delivery of small interfering RNAs with vitamin E-coupled nanoparticles for treating hepatitis C"],"prefix":"10.1038","volume":"6","author":[{"given":"Liang","family":"Duan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,4,26]]},"reference":[{"key":"BFsrep24867_CR1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1001\/jama.2014.7085","volume":"312","author":"A Kohli","year":"2014","unstructured":"Kohli, A., Shaffer, A., Sherman, A. & Kottilil, S. 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