Overview of gene editing strategies against HBV

IF 4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2026-03-01 Epub Date: 2026-01-20 DOI:10.1016/j.antiviral.2026.106355

Zak T. Janetzki , Laura C. McCoullough , Peter A. Revill , Margaret Littlejohn

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引用次数: 0

Abstract

254 million people currently live with chronic hepatitis B virus (HBV) infection, with over 1 million deaths annually due to complications such as cirrhosis and hepatocellular carcinoma. Although current direct-acting antivirals suppress HBV replication, they do not eliminate the virus and rarely lead to HBV functional cure, defined as the loss of serum hepatitis B surface antigen (HBsAg) and DNA. A major barrier to achieving HBV functional cure is the HBV covalently closed circular DNA minichromosome (cccDNA), which hides from the immune system in the nucleus of an infected cell, and is very stable. Another barrier is integration of incomplete HBV genomes into the host genome, which is the main source of HBsAg in later disease stages, and is difficult to target without impacting the human genome. New direct-acting antivirals are required that target different stages of the HBV replication cycle, including the HBV cccDNA and integrated DNA to improve rates of functional cure. The development of gene editing tools provides an opportunity to develop novel therapies that target the HBV cccDNA, integrated DNA and HBV RNA. This review explores the different gene editing tools that have been used to target the HBV cccDNA, integrated DNA and RNA.

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抗HBV基因编辑策略综述

目前有2.54亿人患有慢性乙型肝炎病毒（HBV）感染，每年有100多万人死于肝硬化和肝细胞癌等并发症。虽然目前的直接作用抗病毒药物抑制HBV复制，但它们不能消除病毒，也很少导致HBV功能性治愈，定义为血清乙型肝炎表面抗原（HBsAg）和DNA的丢失。实现HBV功能性治愈的主要障碍是HBV共价闭合环状DNA小染色体（cccDNA），它隐藏在感染细胞的细胞核中，不受免疫系统的影响，并且非常稳定。另一个障碍是将不完整的HBV基因组整合到宿主基因组中，这是疾病后期HBsAg的主要来源，很难在不影响人类基因组的情况下靶向。需要新的直接作用抗病毒药物靶向HBV复制周期的不同阶段，包括HBV cccDNA和整合DNA，以提高功能性治愈率。基因编辑工具的发展为开发针对HBV cccDNA、整合DNA和HBV RNA的新疗法提供了机会。本文综述了用于靶向HBV cccDNA、整合DNA和RNA的不同基因编辑工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.