Gene therapeutic approaches to inhibit hepatitis B virus replication  

作　　者：Maren Gebbing Thorsten Bergmann Eric Schulz Anja Ehrhardt 

机构地区：[1]Institute of Virology and Microbiology,Center for Biomedical Education and Research(ZBAF),Department of Human Medicine,Faculty of Health,University Witten/Herdecke,58453 Witten,Germany

出　　处：《World Journal of Hepatology》2015年第2期150-164,共15页世界肝病学杂志（英文版）（电子版）

基　　金：Supported by The Else-Kröner-Fresenius-Foundation(EKFS)and the UWH Forschungsförderung.

摘　　要：Acute and chronic hepatitis B virus(HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammation of the liver and over years this can lead to cirrhosis and the development of hepatocellularcarcinomas. Currently available therapeutics for chronically infected individuals aim at reducing viral replication and to slow down or stop the progression of the disease. Therefore, novel treatment options are needed to efficiently combat and eradicate this disease. Here we provide a state of the art overview of gene therapeutic approaches to inhibit HBV replication. We discuss non-viral and viral approaches which were explored to deliver therapeutic nucleic acids aiming at reducing HBV replication. Types of delivered therapeutic nucleic acids which were studied since many years include antisense oligodeoxynucleotides and antisense RNA, ribozymes and DNAzymes, RNA interference, and external guide sequences. More recently designer nucleases gained increased attention and were exploited to destroy the HBV genome. In addition we mention other strategies to reduce HBV replication based on delivery of DNA encoding dominant negative mutants and DNA vaccination. In combination with available cell culture and animal models for HBV infection, in vitro and in vivo studies can be performed to test efficacy of gene therapeutic approaches. Recent progress but also challenges will be specified and future perspectives will be discussed. This is an exciting time to explore such approaches because recent successes of gene therapeutic strategies in the clinic to treat genetic diseases raise hope to find alternative treatment options for patients chronically infected with HBV.Acute and chronic hepatitis B virus （HBV） infectionsremain to present a major global health problem. Theinfection can be associated with acute symptomaticor asymptomatic hepatitis which can cause chronicinflammation of the liver and over years this can leadto cirrhosis and the development of hepatocellularcarcinomas. Currently available therapeutics forchronically infected individuals aim at reducing viralreplication and to slow down or stop the progressionof the disease. Therefore, novel treatment options areneeded to efficiently combat and eradicate this disease.Here we provide a state of the art overview of genetherapeutic approaches to inhibit HBV replication. Wediscuss non-viral and viral approaches which wereexplored to deliver therapeutic nucleic acids aiming atreducing HBV replication. Types of delivered therapeuticnucleic acids which were studied since many yearsinclude antisense oligodeoxynucleotides and antisenseRNA, ribozymes and DNAzymes, RNA interference,and external guide sequences. More recently designernucleases gained increased attention and wereexploited to destroy the HBV genome. In addition wemention other strategies to reduce HBV replicationbased on delivery of DNA encoding dominant negativemutants and DNA vaccination. In combination withavailable cell culture and animal models for HBVinfection, in vitro and in vivo studies can be performedto test efficacy of gene therapeutic approaches. Recentprogress but also challenges will be specified andfuture perspectives will be discussed. This is an excitingtime to explore such approaches because recentsuccesses of gene therapeutic strategies in the clinicto treat genetic diseases raise hope to find alternativetreatment options for patients chronically infected withHBV.

关 键 词：Gene therapy Hepatitis B virus Antisense nucleic acid RNA interference Designer nuclease RIBOZYME DNAZYME Dominant negative mutant External guide sequence DNA vaccination 

分 类 号：R512.62[医药卫生—内科学]