Jacobs Ridhwaanah, Singh Prashika, Smith Tiffany, Arbuthnot Patrick, Maepa Mohube Betty
Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Gene Ther. 2025 Jan;32(1):8-15. doi: 10.1038/s41434-022-00342-5. Epub 2022 May 24.
Available treatment for chronic hepatitis B virus (HBV) infection offers modest functional curative efficacy. The viral replicative intermediate comprising covalently closed circular DNA (cccDNA) is responsible for persistent chronic HBV infection. Hence, current efforts have focused on developing therapies that disable cccDNA. Employing gene editing tools has emerged as an attractive strategy, with the end goal of establishing permanently inactivated cccDNA. Although anti-HBV designer nucleases are effective in vivo, none has yet progressed to clinical trial. Lack of safe and efficient delivery systems remains the limiting factor. Several vectors may be used to deliver anti-HBV gene editor-encoding sequences, with viral vectors being at the forefront. Despite the challenges associated with packaging large gene editor-encoding sequences into viral vectors, advancement in the field is overcoming such limitations. Translation of viral vector-mediated gene editing against HBV to clinical application is within reach. This review discusses the prospects of delivering HBV targeted designer nucleases using viral vectors.
慢性乙型肝炎病毒（HBV）感染的现有治疗方法的功能治愈效果有限。由共价闭合环状DNA（cccDNA）组成的病毒复制中间体是导致慢性HBV持续感染的原因。因此，目前的努力集中在开发使cccDNA失活的疗法。使用基因编辑工具已成为一种有吸引力的策略，最终目标是建立永久失活的cccDNA。尽管抗HBV设计核酸酶在体内有效，但尚未有任何一种进入临床试验阶段。缺乏安全有效的递送系统仍然是限制因素。几种载体可用于递送编码抗HBV基因编辑器的序列，其中病毒载体处于领先地位。尽管将大的编码基因编辑器的序列包装到病毒载体中存在挑战，但该领域的进展正在克服这些限制。病毒载体介导的针对HBV的基因编辑向临床应用的转化指日可待。本综述讨论了使用病毒载体递送HBV靶向设计核酸酶的前景。
