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用于治疗乙型肝炎病毒感染的RNA干扰技术。

RNAi for treating hepatitis B viral infection.

作者信息

Chen Yong, Cheng Guofeng, Mahato Ram I

机构信息

Huai-An 4th People's Hospital, Jiangsu, China.

出版信息

Pharm Res. 2008 Jan;25(1):72-86. doi: 10.1007/s11095-007-9504-0. Epub 2007 Dec 12.

DOI:10.1007/s11095-007-9504-0
PMID:18074201
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2217617/
Abstract

Chronic hepatitis B virus (HBV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Current treatment strategies of HBV infection including the use of interferon (IFN)-alpha and nucleotide analogues such as lamivudine and adefovir have met with only partial success. Therefore, it is necessary to develop more effective antiviral therapies that can clear HBV infection with fewer side effects. RNA interference (RNAi), by which a small interfering RNA (siRNA) induces the gene silence at a post-transcriptional level, has the potential of treating HBV infection. The successful use of chemically synthesized siRNA, endogenous expression of small hairpin RNA (shRNA) or microRNA (miRNA) to silence the target gene make this technology towards a potentially rational therapeutics for HBV infection. However, several challenges including poor siRNA stability, inefficient cellular uptake, widespread biodistribution and non-specific effects need to be overcome. In this review, we discuss several strategies for improving the anti-HBV therapeutic efficacy of siRNAs, while avoiding their off-target effects and immunostimulation. There is an in-depth discussion on the (1) mechanisms of RNAi, (2) methods for siRNA/shRNA production, (3) barriers to RNAi-based therapies, and (4) delivery strategies of siRNA for treating HBV infection.

摘要

慢性乙型肝炎病毒（HBV）感染是肝硬化和肝细胞癌（HCC）的主要病因之一。目前HBV感染的治疗策略，包括使用α干扰素（IFN）以及核苷类似物如拉米夫定和阿德福韦，仅取得了部分成功。因此，有必要开发更有效的抗病毒疗法，以更少的副作用清除HBV感染。RNA干扰（RNAi），即小干扰RNA（siRNA）在转录后水平诱导基因沉默，具有治疗HBV感染的潜力。化学合成的siRNA、小发夹RNA（shRNA）或微小RNA（miRNA）的内源性表达成功用于沉默靶基因，使该技术有望成为治疗HBV感染的合理疗法。然而，包括siRNA稳定性差、细胞摄取效率低、广泛的生物分布和非特异性效应等几个挑战需要克服。在这篇综述中，我们讨论了几种提高siRNA抗HBV治疗效果的策略，同时避免其脱靶效应和免疫刺激。文中对（1）RNAi机制、（2）siRNA/shRNA产生方法、（3）基于RNAi疗法的障碍以及（4）用于治疗HBV感染的siRNA递送策略进行了深入讨论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/540d22f1c3ba/11095_2007_9504_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/f2285669b6c7/11095_2007_9504_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/d4526575993f/11095_2007_9504_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/ceb865b0bc24/11095_2007_9504_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/540d22f1c3ba/11095_2007_9504_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/f81f84304bc1/11095_2007_9504_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/2d61fc7483e3/11095_2007_9504_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/ef22cc1e92c8/11095_2007_9504_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/f2285669b6c7/11095_2007_9504_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/d4526575993f/11095_2007_9504_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/ceb865b0bc24/11095_2007_9504_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1256/2217617/540d22f1c3ba/11095_2007_9504_Fig7_HTML.jpg

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