Towards HBV curative therapies

• Type of Material: Article
• Authors: Raymond F Schinazi, Emory University; Leda Bassit, Emory University; Maryam Ehteshami, Emory University; Tarik Asselah, University of Paris Diderot
• Language: English
• Date: 2018-02-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/liv.13656
• Title of Journal or Parent Work: Liver International
• ISSN: 1478-3223
• Volume: 38
• Start Page: 102
• End Page: 114
• Grant/Funding Information: This work was supported by NIH grant 1R01-AI-132833; and in part by funding from the NIH funded Emory Center for AIDS Research grant P30-AI-050409 to RFS.
• Keywords: EFFECTOR NUCLEASES; AGONIST GS-9620; Science & Technology; INHIBITOR MYRCLUDEX-B; HEPATITIS-B-VIRUS; HBSAG QUANTIFICATION; immunotherapy; HBV cure; Gastroenterology & Hepatology; TENOFOVIR ALAFENAMIDE; INFECTION; NATURAL-HISTORY; ANTIGEN-POSITIVE PATIENTS; Life Sciences & Biomedicine; antiviral agents; IN-VIVO; cccDNA
• Research Categories: Biology, Virology; Health Sciences, Medicine and Surgery

Abstract

Tremendous progress has been made over the last 2 decades to discover and develop approaches to control hepatitis B virus (HBV) infections and to prevent the development of hepatocellular carcinoma using various interferons and small molecules as antiviral agents. However, none of these agents have significant impact on eliminating HBV from infected cells. Currently the emphasis is on silencing or eliminating cccDNA, which could lead to a cure for HBV. Various approaches are being developed including the development of capsid effectors, CRISPR/Cas9, TALENS, siRNA, entry and secretion inhibitors, as well as immunological approaches. It is very likely that a combination of these modalities will need to be employed to successfully eliminate HBV or prevent virus rebound on discontinuation of therapy. In the next 5 years clinical data will emerge which will provide insight on the safety and feasibility of these approaches and if they can be applied to eradicate HBV infections globally. In this review, we summarize current treatments and we highlight and examine recent therapeutic strategies that are currently being evaluated at the preclinical and clinical stage.