Gene therapeutic approaches to inhibit hepatitis B virus replication.
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 hepatocellular carcinomas. 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.
Maren Gebbing, Thorsten Bergmann, Eric Schulz, Anja Ehrhardt, 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.
Maren
M
Gebbing
Maren Gebbing, Thorsten Bergmann, Eric Schulz, Anja Ehrhardt, 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.
Thorsten
T
Bergmann
Maren Gebbing, Thorsten Bergmann, Eric Schulz, Anja Ehrhardt, 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.
Eric
E
Schulz
Maren Gebbing, Thorsten Bergmann, Eric Schulz, Anja Ehrhardt, 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.
Anja
A
Ehrhardt
Antisense nucleic acid; DNA vaccination; DNAzyme; Designer nuclease; Dominant negative mutant; External guide sequence; Gene therapy; Hepatitis B virus; RNA interference; Ribozyme