Understanding the antiviral effects of RNAi-based therapy on chronic hepatitis B infection

Sarah Kadelka, Harel Dahari, Stanca M Ciupe

BIORXIV

July 2020

Abstract

With about 300 million persons infected worldwide and 800,000 deaths annually, chronic infection with hepatitis B virus (HBV) is a major public health burden with high endemic areas around the world. Current treatment options focus on removing circulating HBV DNA but are suboptimal in removing hepatitis B s- and e-antigens. ARC-520, a RNA interference drug, had induced substantial hepatitis B s- and e- antigen reductions in animals and patients receiving therapy. We study the effect of ARC-520 on hepatitis B s- and e-antigen decline by developing mathematical models for the dynamics of intracellular and serum viral replication, and compare it to patient HBV DNA, hepatitis B s- and e-antigen data from a clinical trial with one ARC-520 injection and daily nucleoside analogue therapy. We examine biological parameters describing the different phases of HBV DNA, s-antigen and e-antigen decline and rebound after treatment initiation, and estimate treatment effectiveness. Such approach can inform the RNA interference drug therapy.

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Loyola University Medical Center

Department of Medicine

Division of Hepatology

2160 S. First Ave
Mulcahy Center, Rm 1610

Maywood, IL 60153, USA

Email: hdahari@luc.edu

Phone: 708-216-4682

Fax: 708-216-6299