Oligonucleotide-Based Therapies for Chronic HBV Infection: A Primer on Biochemistry, Mechanisms and Antiviral Effects
by Andrew Vaillant
[ORCID]
Replicor Inc., 6100 Royalmount Avenue, Montreal, QC H4P 2R2, Canada
Academic Editors: Mark W. Douglas and Thomas Tu
Viruses 2022, 14(9), 2052; https://doi.org/10.3390/v14092052
Received: 11 August 2022 / Revised: 8 September 2022 / Accepted: 8 September 2022 / Published: 16 September 2022
(This article belongs to the Special Issue Hepatitis B Virus: New Breakthroughs to Conquer an Ancient Disease)
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Abstract
Three types of oligonucleotide-based medicines are under clinical development for the treatment of chronic HBV infection. Antisense oligonucleotides (ASOs) and synthetic interfering RNA (siRNA) are designed to degrade HBV mRNA, and nucleic acid polymers (NAPs) stop the assembly and secretion of HBV subviral particles. Extensive clinical development of ASOs and siRNA for a variety of liver diseases has established a solid understanding of their pharmacodynamics, accumulation in different tissue types in the liver, pharmacological effects, off-target effects and how chemical modifications and delivery approaches affect these parameters. These effects are highly conserved for all ASO and siRNA used in human studies to date. The clinical assessment of several ASO and siRNA compounds in chronic HBV infection in recent years is complicated by the different delivery approaches used. Moreover, these assessments have not considered the large clinical database of ASO/siRNA function in other liver diseases and known off target effects in other viral infections. The goal of this review is to summarize the current understanding of ASO/siRNA/NAP pharmacology and integrate these concepts into current clinical results for these compounds in the treatment of chronic HBV infection. View Full-Text
Keywords: NAP; ASO; siRNA; HBsAg; functional cure; immunostimulation 作者: StephenW 时间: 2022-9-24 15:38
