Advances with RNAi-Based Therapy for Hepatitis B Virus Infection

• Published in: Viruses Vol. 12; no. 8; p. 851
• Main Authors: van den Berg, Fiona, Limani, Shonisani Wendy, Mnyandu, Njabulo, Maepa, Mohube Betty, Ely, Abdullah, Arbuthnot, Patrick
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.08.2020; MDPI
• Subjects: Animals; Antigens; cccDNA; chemical bonding; Chronic infection; Circular DNA; Cirrhosis; Clinical Trials as Topic; CRISPR; Deoxyribonucleic acid; DNA; DNA, Circular; DNA, Viral - genetics; Endoplasmic reticulum; Fibrosis; Gene expression; Gene Silencing; genes; Genetic Vectors; HBV; Hepatitis; Hepatitis B; Hepatitis B - complications; Hepatitis B - therapy; Hepatitis B virus; Hepatocellular carcinoma; hepatoma; Humans; Infections; Infectivity; liver; Liver - pathology; Liver - virology; Liver cancer; Liver cirrhosis; Mice; MicroRNAs; miRNA; mortality; pathogenicity; people; Proteins; Replication; Review; risk; RNA interference; RNA-mediated interference; RNAi; RNAi Therapeutics - methods; RNAi Therapeutics - trends; shRNA; siRNA; therapeutics; vaccines; virus replication; Virus Replication - genetics; miRNA; RNAi; siRNA; cccDNA; shRNA; HBV
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v12080851

Infection with hepatitis B virus (HBV) remains a global health challenge. Approximately 292 million people worldwide are chronically infected with HBV and the annual mortality from the infection is approaching 900,000. Despite the availability of an effective prophylactic vaccine, millions of individuals are at risk of potentially fatal complicating cirrhosis and hepatocellular carcinoma. Current drug treatments can suppress viral replication, slow the progression of liver fibrosis, and reduce infectivity, but can rarely clear the viral covalently closed circular DNA (cccDNA) that is responsible for HBV persistence. Alternative therapeutic strategies, including those based on viral gene silencing by harnessing the RNA interference (RNAi) pathway, effectively suppress HBV replication and thus hold promise. RNAi-based silencing of certain viral genes may even lead to disabling of cccDNA during chronic infection. This review summarizes different RNAi activators that have been tested against HBV, the advances with vectors used to deliver artificial potentially therapeutic RNAi sequences to the liver, and the current status of preclinical and clinical investigation.