治愈 HBV 的潜力:CRISPR 介导的 HBV 基因干扰概述。

IF 4.9 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Frontiers in genome editing Pub Date : 2024-10-09 eCollection Date: 2024-01-01 DOI:10.3389/fgeed.2024.1467449
Zhi Q Yao, Madison B Schank, Juan Zhao, Mohamed El Gazzar, Ling Wang, Yi Zhang, Addison C Hill, Puja Banik, Jaeden S Pyburn, Jonathan P Moorman
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引用次数: 0

摘要

乙型肝炎病毒(HBV)感染是全球肝病的常见病因。目前使用核苷酸类似物(NAs)进行的抗病毒治疗只能抑制新的 HBV 复制,但无法消除慢性 HBV 感染,因为持续存在的共价闭合环状(ccc)DNA 可维持病毒复制。CRISPR/Cas9系统是一种新型基因组编辑工具,可以精确地破坏和灭活基因。CRISPR/Cas9 系统高效简便,已被用于多项研究,特异性地破坏 HBV 基因组,在体外和体内产生不同的抗 HBV 作用。此外,多焦点基因打靶也显示出更强的抗病毒活性,为破坏和灭活 HBV cccDNA 以及整合的 HBV DNA 的联合疗法铺平了道路。尽管该技术具有良好的抗病毒效果,但在临床应用前仍面临着一些需要克服的挑战,即脱靶效应和体内给药。因此,需要提高 CRISPR/Cas9 的效率、特异性、多功能性和给药方式。在此,我们对最近的文献进行了批判性的回顾,这些文献描述了设计靶向 HBV 基因组的引导 RNA(gRNA)所使用的工具、表达和递送 CRISPR/Cas9 成分所使用的载体、评估 CRISPR 介导的 HBV 基因破坏所使用的模型、评估 CRISPR/Cas9 介导的 HBV 基因破坏所诱导的抗病毒和脱靶效应所使用的方法,以及利用这种 HBV 基因编辑方法的未来方向和挑战的前景,从而推动 HBV 治疗走向临床治愈。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The potential of HBV cure: an overview of CRISPR-mediated HBV gene disruption.

Hepatitis B virus (HBV) infection is a common cause of liver disease worldwide. The current antiviral treatment using nucleotide analogues (NAs) can only suppress de novo HBV replication but cannot eliminate chronic HBV infection due to the persistence of covalently closed circular (ccc) DNA that sustains viral replication. The CRISPR/Cas9 system is a novel genome-editing tool that enables precise gene disruption and inactivation. With high efficiency and simplicity, the CRISPR/Cas9 system has been utilized in multiple studies to disrupt the HBV genome specifically, eliciting varying anti-HBV effects both in vitro and in vivo. Additionally, multi-locus gene targeting has shown enhanced antiviral activity, paving the way for combination therapy to disrupt and inactivate HBV cccDNA as well as integrated HBV DNA. Despite its promising antiviral effects, this technology faces several challenges that need to be overcome before its clinical application, i.e., off-target effects and in vivo drug delivery. As such, there is a need for improvement in CRISPR/Cas9 efficiency, specificity, versatility, and delivery. Here, we critically review the recent literature describing the tools employed in designing guide RNAs (gRNAs) targeting HBV genomes, the vehicles used for expressing and delivering CRISPR/Cas9 components, the models used for evaluating CRISPR-mediated HBV gene disruption, the methods used for assessing antiviral and off-target effects induced by CRISPR/Cas9-mediated HBV gene disruption, and the prospects of future directions and challenges in leveraging this HBV gene-editing approach, to advance the HBV treatment toward a clinical cure.

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CiteScore
7.00
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