REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Infectious Diseases
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1633001
Small nucleic acid drugs-The dawn of functional cure of chronic hepatitis B
Provisionally accepted
- Xixi Hospital of Hangzhou, Hangzhou, China
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Chronic hepatitis B (CHB), a chronic liver infectious disease, results from persistent hepatitis B virus (HBV) infection lasting over six months. It has become a substantial global public health burden. CHB is often manifested by concomitant hepatic biochemical abnormalities, and/or notable inflammatory necrosis, and/or liver histological fibrosis. If left uncontrolled, CHB can progress to severe liver diseases and may even lead to death. Although currently approved therapeutic agents can effectively suppress viral replication and, to a certain extent, reduce related complications, their ineffectiveness in targeting covalently closed circular DNA (cccDNA) fundamentally restricts their potential to achieve a clinical cure. In recent years, research focused on attaining a functional cure for CHB has been on the rise. Drugs with different targeting mechanisms and diverse therapeutic strategies have rendered a clinical cure for CHB a possibility. Among these, emerging small nucleic acid drugs show great promise, exhibiting high potential for achieving a sustained functional cure. In this review, we systematically investigate the unique structure of the HBV genome. Moreover, we delve into the classification, mechanisms of action, and pathways for small nucleic acid drugs used in CHB treatment to achieve a functional cure. Additionally, we analyze some challenges encountered in the development of these drugs and propose corresponding solutions. Furthermore, we discuss current clinical studies and combination therapies involving small nucleic acid drugs for CHB treatment.
Keywords: Chronic hepatitis B, RNA Interference, small interfering RNA, microRNA, antisenseoligonucleotides, functional cure, small nucleic acid drugs
Received: 22 May 2025; Accepted: 17 Sep 2025.
Copyright: © 2025 Zhang, Cao, Zhuang, Sun, Tong, Xi, Liu and Zhuang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jianjun Xi, xjianjun@foxmai.com
Shourong Liu, lsr85463990@126.com
Rangxiao Zhuang, 18958191205@163.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.