Research advances in clinical translation of RNA interference against hepatitis B virus infection

Dou Yunxiao; Yan Jiajun; Wu Zhongjun

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Research advances in clinical translation of RNA interference against hepatitis B virus infection

更新时间：2026-10-23

- Research advances in clinical translation of RNA interference against hepatitis B virus infection
- Journal of Chongqing Medical University Pages: 1-4(2026)
- 作者机构：
  
  1.重庆医科大学第一临床学院，重庆 400016
  2.重庆医科大学附属第一医院肝胆外科，重庆 400010
- 作者简介：
- 基金信息：
- DOI：
  CLC： R512.62
- Received：02 September 2026，
  
  Revised：2026-09-23，
  
  Accepted：24 September 2026，
  
  Published：23 October 2026
- 稿件说明：
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Dou Yunxiao,Yan Jiajun,Wu Zhongjun.Research advances in clinical translation of RNA interference against hepatitis B virus infection[J].Journal of Chongqing Medical University,
DOI：

Dou Yunxiao,Yan Jiajun,Wu Zhongjun.Research advances in clinical translation of RNA interference against hepatitis B virus infection[J].Journal of Chongqing Medical University, DOI：10.13406/j.cnki.cyxb..

摘要

慢性乙型肝炎（chronic hepatitis B，CHB）全球疾病负担沉重，现有药物如核苷（酸）类似物与干扰素等无法抑制或直接清除共价闭合环状DNA（covalently closed circular DNA，cccDNA），难以实现CHB的功能性治愈。近年来RNA干扰（RNA interference，RNAi）为CHB的功能性治愈提供了新策略，但相关研究仍缺少系统性的总结。本文通过检索Web of Science、PubMed等数据库近年来的相关中英文文献，系统归纳RNA干扰靶向治疗慢性乙型肝炎的临床研究进展。文献分析显示，目前N-乙酰半乳糖胺（N-acetylgalactosamine，GalNAc）偶联小干扰RNA（small interfering RNA，siRNA）、反义寡核苷酸（antisense oligonucleotide，ASO）已进入临床后期研究阶段，但两类药物单药均难以清除核内cccDNA，停药复发率偏高；工程化外泌体突破核内递送瓶颈的临床前证据已得到验证。本综述可为未来进一步优化核酸药物联用方案、推进工程化外泌体的临床转化提供参考，并助力CHB实现功能性治愈。

Abstract

Chronic hepatitis B（CHB） imposes a substantial global disease burden. Existing therapies，such as nucleos（t）ide analogs and interferon，are unable to inhibit or directly eliminate covalently closed circular DNA（cccDNA），making it challenging to achieve a functional cure of CHB. In recent years，RNA interference has provided a novel strategy for the functional cure of CHB，yet there remains a lack of systematic synthesis of relevant research. This study systematically reviewed recent literature in Chinese and English retrieved from databases such as Web of Science and PubMed to summarize clinical research advances in RNA interference-based targeted therapy for CHB. The literature analysis reveals that N-acetylgalactosamine-conjugated small interfering RNA and antisense oligonucleotide therapies have entered late-stage clinical trials； however，neither class，when used alone，can readily eliminate nuclear cccDNA，and relapse rates after treatment discontinuation are relatively high. Preclinical studies have provided evidence that engineered exosomes can overcome barriers to nuclear delivery. This review may inform the further optimization of nucleic acid-based combination regimens and the clinical translation of engineered exosomes，thereby supporting efforts to achieve a functional cure of CHB.

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references

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