An RNA-based system to study hepatitis B virus replication and evaluate antivirals

Abstract

Hepatitis B virus (HBV) chronically infects an estimated 300 million people, and standard treatments are rarely curative. Infection increases the risk of liver cirrhosis and hepatocellular carcinoma, and consequently, nearly 1 million people die each year from chronic hepatitis B. Tools and approaches that bring insights into HBV biology and facilitate the discovery and evaluation of antiviral drugs are in demand. Here, we describe a method to initiate the replication of HBV, a DNA virus, using synthetic RNA. This approach eliminates contaminating background signals from input virus or plasmid DNA that plagues existing systems and can be used to study multiple stages of HBV replication. We further demonstrate that this method can be uniquely applied to identify sequence variants that confer resistance to antiviral drugs.

Chemically Modified Platforms for Better RNA Therapeutics

“…This prolonged effectiveness allows for reduced dosing frequency, resulting in improved patient compliance. The extended duration of action gives RNA-based drugs a competitive edge in the therapy of multitudinous diseases, including cardiovascular diseases, metabolic diseases, liver diseases, and multiple rare diseases. − Recently, there has been a significant acceleration in the approval of RNA-based drugs in clinical settings, demonstrating remarkable therapeutic efficacy (Table ). As a result, RNA-based drugs have garnered substantial attention and are poised to become the third major category of drugs, alongside small molecule chemicals and antibodies.…”