Gene therapeutic approaches to inhibit hepatitis B virusreplication
摘要
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.