基于RNAi的乙型肝炎病毒感染疗法的研究进展

StephenW

Advances with RNAi-Based Therapy for Hepatitis B Virus Infection
by Fiona van den Berg [OrcID] , Shonisani Wendy Limani, Njabulo Mnyandu, Mohube Betty Maepa, Abdullah Ely and Patrick Arbuthnot * [OrcID]
Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(8), 851; https://doi.org/10.3390/v12080851
Received: 30 June 2020 / Revised: 22 July 2020 / Accepted: 29 July 2020 / Published: 4 August 2020
(This article belongs to the Special Issue RNA Interference (RNAi) for Antiviral Therapy)
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Abstract
Infection with hepatitis B virus (HBV) remains a global health challenge. Approximately 292 million people worldwide are chronically infected with HBV and the annual mortality from the infection is approaching 900,000. Despite the availability of an effective prophylactic vaccine, millions of individuals are at risk of potentially fatal complicating cirrhosis and hepatocellular carcinoma. Current drug treatments can suppress viral replication, slow the progression of liver fibrosis, and reduce infectivity, but can rarely clear the viral covalently closed circular DNA (cccDNA) that is responsible for HBV persistence. Alternative therapeutic strategies, including those based on viral gene silencing by harnessing the RNA interference (RNAi) pathway, effectively suppress HBV replication and thus hold promise. RNAi-based silencing of certain viral genes may even lead to disabling of cccDNA during chronic infection. This review summarizes different RNAi activators that have been tested against HBV, the advances with vectors used to deliver artificial potentially therapeutic RNAi sequences to the liver, and the current status of preclinical and clinical investigation. View Full-Text
Keywords: HBV; RNAi; siRNA; shRNA; miRNA; cccDNA

StephenW

基于RNAi的乙型肝炎病毒感染疗法的研究进展
作者：Fiona van den Berg [OrcID]，Shonisani Wendy Limani，Njabulo Mnyandu，Mohube Betty Maepa，Abdullah Ely和Patrick Arbuthnot * [OrcID]
威特沃特斯兰德大学卫生科学学院病理学学院Wits / SAMRC抗病毒基因治疗研究室，南非约翰内斯堡2050
*
应与之联系的作者。
病毒2020，12（8），851; https://doi.org/10.3390/v12080851
收到：2020年6月30日/修订：2020年7月22日/接受：2020年7月29日/发布：2020年8月4日
（本文属于针对抗病毒治疗的特刊RNA干扰（RNAi））
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抽象
乙型肝炎病毒（HBV）感染仍然是全球健康挑战。全球约有2.92亿人长期感染HBV，每年因感染而导致的死亡率接近90万。尽管可获得有效的预防性疫苗，但仍有数以百万计的人有可能致命并发肝硬化和肝细胞癌。当前的药物治疗可以抑制病毒复制，减慢肝纤维化的进程，并降低感染性，但很少清除引起HBV持久性的病毒共价闭合环状DNA（cccDNA）。替代治疗策略，包括利用RNA干扰（RNAi）途径基于病毒基因沉默的策略，可有效抑制HBV复制，因此前景广阔。某些病毒基因的基于RNAi的沉默甚至可能导致慢性感染过程中cccDNA失能。这篇综述总结了已针对HBV进行测试的不同RNAi激活剂，用于将人工潜在治疗性RNAi序列递送至肝脏的载体的进展以及临床前和临床研究的现状。查看全文
关键字：乙肝病毒； RNAi； siRNA; shRNA; miRNA;基因

StephenW

https://www.mdpi.com/1999-4915/12/8/851/htm