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Hepatol Res. 2014 Aug;44(8):897-906. doi: 10.1111/hepr.12189. Epub 2013 Jul 21.
Targeted delivery of siRNA against hepatitis B virus by preS1 peptide molecular ligand.Huang W1, Li X, Yi M, Zhu S, Chen W.
Author information
- 1Department of Laboratory Medicine, the Second Hospital Affiliated to Chongqing Medical University, Chongqing, China.
AbstractAIM: For chronic hepatitis B virus (HBV) infection, the effects of current therapies are limited. RNA interference of virus-specific genes has emerged as a potential antiviral mechanism. However, a suitable delivery vector is still to be developed. We studied a novel vector transferring siRNA targeting hepatic cells in vivo and in vitro in order to find a new way to cure HBV-related live diseases.
METHODS: The preS1-9Arg ligand was used to deliver siRNA to HepG2 and to HepG2 2.2.15 cells. To validate the antiviral efficacy in vivo, a HBV viremic animal model was established by s.c. inoculation of HepG2 2.2.15 tumor cells in nude mice. The minimal retardation effect on the migration of siRNA was detected by gel electrophoresis to confirm the combination and the optimal ratio. Hepatitis B surface antigen (HBsAg) levels were detected by semiquantitatively enzyme-linked immunosorbent assay RNA levels were quantified with quantitative real-time polymerase chain reaction and protein levels were determined with immunoblots and immunohistochemistry.
RESULTS: PreS1-9Arg peptide strongly combined and transferred siRNA into HepG2 cells. PreS1-9Arg-siRNA molecular conjugate effectively reduced the production of HBsAg and HBV DNA without liver toxicity in vitro and in vivo.
CONCLUSION: The results indicated that preS1-9Arg may be a potential novel vector to deliver siRNA targeting liver cells.
© 2013 The Japan Society of Hepatology.
KEYWORDS: RNA interference; hepatitis B virus; molecular ligand; preS1
肝脏Res
。 2014年八月，44（8）：897-906。 DOI：10.1111/ hepr.12189。 EPUB2013年07月21。
靶向递送的siRNA的抗乙型肝炎病毒前S1通过肽分子配体。
黄W1，李X，屹男，朱S，W·陈
作者信息
教研室实验室医学，第二附属重庆医科大学，重庆，中国的医院。
摘要
目的：
用于慢性乙型肝炎病毒（HBV）感染，目前的治疗方法的效果是有限的。病毒特异基因的RNA干扰已经成为一个潜在的抗病毒机制。然而，合适的递送载体仍然有待开发。我们研究了一种新的载体传递的siRNA，以寻找新的方法来治疗乙肝相关疾病的活肝靶向细胞在体内和体外。
方法：
该preS1-9Arg配体用于siRNA递送至HepG2和对HepG22.2.15细胞。为了验证在体内的抗病毒疗效中，乙肝病毒血症动物模型，通过建立SC接种的HepG22.2.15细胞瘤裸鼠体内。通过凝胶电泳检测的siRNA的有迁移的最小相位差效果进行确认的组合的最佳比例。通过半定量酶联免疫吸附测定RNA水平检测乙型肝炎表面抗原（HBsAg）的含量进行定量和实时定量聚合酶链式反应和蛋白质水平进行了测定和免疫印迹和免疫组化分析。
结果：
PreS1-9Arg肽强烈结合并转移到siRNA的HepG2细胞。 PreS1-9Arg-siRNA的分子缀合物有效地降低了生产的HBsAg和HBV DNA的无肝毒性的体外和体内。
结论：
结果表明，preS1-9Arg可以是潜在的新的载体siRNA递送靶向肝细胞。
©肝脏病杂志2013年日本社会。
关键词：
RNA干扰;乙型肝炎病毒;分子配体;前S
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发表于 2014-8-31 20:33
