Cancer Research Center of Lyon, INSERM U1052, CNRS UMR 5286, 69008 Lyon, France.
The Lyon Hepatology Institute EVEREST, 69003 Lyon, France.
Viruses. 2024 Oct 2;16(10):1565. doi: 10.3390/v16101565.
Hepatitis B virus (HBV) infection remains a significant global health challenge, leading to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) and integrated HBV DNA are pivotal in maintaining viral persistence. Recent advances in CRISPR/Cas technology offer innovative strategies to inhibit HBV by directly targeting both cccDNA and integrated HBV DNA or indirectly by degrading HBV RNAs or targeting host proteins. This review provides a comprehensive overview of the latest advancements in using CRISPR/Cas to inhibit HBV, with a special highlight on newer non-double-strand (non-DSB) break approaches. Beyond the canonical use of CRISPR/Cas for target inhibition, we discuss additional applications, including HBV diagnosis and developing models to understand cccDNA biology, highlighting the diverse use of this technology in the HBV field.
乙型肝炎病毒 (HBV) 感染仍然是一个重大的全球健康挑战,可导致慢性肝炎、肝硬化和肝细胞癌 (HCC)。共价闭合环状 DNA (cccDNA) 和整合的 HBV DNA 是维持病毒持续存在的关键。CRISPR/Cas 技术的最新进展提供了通过直接靶向 cccDNA 和整合的 HBV DNA 或间接通过降解 HBV RNA 或靶向宿主蛋白来抑制 HBV 的创新策略。这篇综述全面概述了使用 CRISPR/Cas 抑制 HBV 的最新进展,特别强调了较新的非双链 (non-DSB) 断裂方法。除了 CRISPR/Cas 的经典靶抑制用途外,我们还讨论了其他应用,包括 HBV 诊断和开发模型以了解 cccDNA 生物学,突出了该技术在 HBV 领域的多种用途。