基于共价闭合环状DNA动力学的慢性乙型肝炎治疗策略

胡接力; 黄爱龙

doi:10.12449/JCH260103

基于共价闭合环状DNA动力学的慢性乙型肝炎治疗策略

DOI: 10.12449/JCH260103

胡接力,
黄爱龙^, ,

重庆医科大学感染性疾病分子生物学教育部重点实验室，重庆 400016

基金项目:

国家重点研发计划 (2022YFA1303600);

国家自然科学基金重点项目 (82530076);

国家自然科学基金面上项目 (82470634)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：胡接力负责撰写文章；黄爱龙负责修改并审校。

详细信息

通信作者:
黄爱龙， ahuang1964@163.com （ORCID：0000-0003-2225-9550）

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出版历程
- 收稿日期: 2025-11-03
- 录用日期: 2025-11-30
- 出版日期: 2026-01-25

Treatment strategies for chronic hepatitis B based on covalently closed circular DNA dynamics

Jieli HU,
Ailong HUANG^{,
,}

Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education，Chongqing Medical University，Chongqing 400016，China

Research funding:

National Key R&D Program of China (2022YFA1303600);

Key Project of National Natural Science Foundation of China (82530076);

General Project of National Natural Science Foundation of China (82470634)

More Information

Corresponding author: HUANG Ailong， ahuang1964@163.com （ORCID： 0000-0003-2225-9550）

摘要

摘要: 实现慢性乙型肝炎病毒（HBV）感染的普遍治愈，是乙型肝炎研究领域的最高目标。深入探索HBV感染治愈的可能途径，对于明确关键研究方向具有重要意义。共价闭合环状DNA（cccDNA）作为HBV复制循环中最难以被清除的遗传物质，既是实现治愈的主要障碍，也是构建治愈策略分析框架的核心基点。本文在概述“cccDNA动力学”思维框架的基础上，进一步阐释其核心内涵，并以此为依据系统探讨论述促进cccDNA衰减的关键策略。
- 乙型肝炎病毒 /
- 共价闭合环状DNA /
- 治疗学
Abstract: Cure of chronic hepatitis B virus （HBV） infection is the ultimate goal in HBV-related research， and exploring potential curative pathways may help to identify key research directions. Covalently closed circular DNA （cccDNA）， as the most difficult genetic material to be eliminated within the HBV replication cycle， is not only a primary impediment to achieving cure， but also a key issue for establishing an analytical framework for cure strategies. This article reviews the thinking framework of “cccDNA dynamics”， further elaborates on its core implications， and systematically discusses the main strategies to promote cccDNA decay.
- Hepatitis B Virus /
- Covalently Closed Circular DNA /
- Therapeutics

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注： a，HBV和HCV复制周期中关键遗传物质的动力学差异导致直接抗病毒药物的疗效差异；b，从cccDNA动力学角度分类抗乙型肝炎药物（部分药物可以发挥两种作用）。HCV，丙型肝炎病毒；HBV，乙型肝炎病毒；rcDNA，松弛双链环状DNA；pgRNA，前基因组RNA；cccDNA，共价闭合环状DNA；siRNA，小干扰RNA；抗-HBs，乙型肝炎病毒表面抗体；preS 1，前S1蛋白；ASO，反义寡核苷酸；TCR-T，T细胞受体工程化T细胞；CAR-T，嵌合抗原受体T细胞。

图 1 基于cccDNA动力学分析慢性乙型肝炎治疗策略

Figure 1. Analysis of treatment strategies for chronic hepatitis B based on cccDNA kinetics

下载: 全尺寸图片幻灯片

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