HIV AND HEPATITIS B CURE: Edited by Sharon R. Lewin and Peter A. RevillRecent developments with advancing gene therapy to treat chronic infection with hepatitis B virusMaepa, Mohube B.; Jacobs, Ridhwaanah; van den Berg, Fiona; Arbuthnot, PatrickAuthor Information Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Health Sciences Faculty, University of the Witwatersrand, Johannesburg, South Africa Correspondence to Patrick Arbuthnot, Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Health Sciences Faculty, University of the Witwatersrand, Johannesburg, South Africa. Tel: +27 0 11 717 2365; fax: +27 0 11 717 2395; e-mail: Patrick.Arbuthnot@wits.ac.za Current Opinion in HIV and AIDS: May 2020 - Volume 15 - Issue 3 - p 200-207 doi: 10.1097/COH.0000000000000623 Buy Metrics Abstract Purpose of review The available vaccine and therapies against hepatitis B virus (HBV) rarely eliminate chronic infection with the virus. High mortality resulting from complicating cirrhosis and hepatocellular carcinoma makes improving anti-HBV therapy an important priority. Recent advances with using gene therapy to counter HBV have potential and are the focus of this review. Recent findings The stable replication-competent HBV intermediate comprising covalently closed circular DNA (cccDNA) is the template for expression of all viral genes. Inactivating cccDNA has thus been a focus of research aimed at achieving cure for HBV infection. Many studies have reported profound inhibition of replication of the virus using silencing and editing techniques. Therapeutic gene silencing with synthetic short interfering RNA is now in clinical trials. Ability to mutate and permanently inactivate cccDNA with engineered gene editors, such as those derived from CRISPR/Cas or TALENs, is particularly appealing but has not yet reached clinical evaluation. Summary Gene silencing and gene editing potentially provide the means to cure HBV infection. However, achieving efficient delivery of therapeutic sequences, ensuring their specificity of action and progress with other antiviral strategies are likely to determine utility of gene therapy for chronic HBV infection. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.