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环状RNA作为病毒感染的治疗方式及克服关键挑战的创新策略:综述

Circular RNAs as a therapeutic modality for viral infections and innovative strategies to overcome key challenges: A review.

作者信息

Hussen Bashdar Mahmud, Abdullah Snur Rasool, Khudhur Zhikal Omar, Samsami Majid, Taheri Mohammad

机构信息

Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil, Iraq; Department of Medical Laboratory Science, College of Health Sciences, Lebanese French University, Kurdistan Region, Erbil, Iraq.

Department of Medical Laboratory Science, College of Health Sciences, Lebanese French University, Kurdistan Region, Erbil, Iraq.

出版信息

Int J Biol Macromol. 2025 Jul;318(Pt 2):145088. doi: 10.1016/j.ijbiomac.2025.145088. Epub 2025 Jun 9.

DOI:10.1016/j.ijbiomac.2025.145088
PMID:40499865
Abstract

Circular RNAs (circRNAs) are small noncoding RNAs with covalently closed loop structures, offering high stability and resistance to exonuclease degradation-traits that make them promising for diagnostic and therapeutic use. CircRNAs participate in diverse cellular processes, including acting as microRNA (miRNA) sponges, modulating transcription, binding RNA-binding proteins (RBPs), regulating translation, and influencing immune responses. Emerging evidence links circRNAs to viral infections, such as HBV, HCV, influenza A virus, and EBV, where altered circRNA expression affects viral replication, immune evasion, and host responses via the circRNA/miRNA/mRNA axis. This review highlights the diagnostic and therapeutic potential of circRNAs in viral infections. We examine their roles in viral pathogenesis, focusing on their mechanisms, regulatory networks, and interactions with host and viral components. CircRNAs show differential expression in viral versus non-viral conditions, making them promising biomarkers for early diagnosis and disease stratification. They may also support vaccine development or serve as tools in antiviral gene therapies. Despite their promise, challenges persist-such as optimizing in vitro synthesis, improving delivery (e.g., lipid nanoparticles), and minimizing immunogenicity and off-target effects. Continued research is essential to refine delivery methods and validate circRNA-based strategies in clinical models.

摘要

环状RNA(circRNAs)是具有共价闭合环状结构的小型非编码RNA,具有高稳定性且能抵抗核酸外切酶降解,这些特性使其在诊断和治疗应用方面颇具前景。circRNAs参与多种细胞过程,包括充当微小RNA(miRNA)海绵、调节转录、结合RNA结合蛋白(RBPs)、调控翻译以及影响免疫反应。新出现的证据将circRNAs与病毒感染联系起来,如乙肝病毒(HBV)、丙肝病毒(HCV)、甲型流感病毒和爱泼斯坦-巴尔病毒(EBV),其中circRNA表达的改变通过circRNA/miRNA/mRNA轴影响病毒复制、免疫逃逸和宿主反应。本综述重点介绍了circRNAs在病毒感染中的诊断和治疗潜力。我们研究了它们在病毒发病机制中的作用,重点关注其机制、调控网络以及与宿主和病毒成分的相互作用。circRNAs在病毒感染与非病毒感染条件下表现出差异表达,这使其有望成为早期诊断和疾病分层的生物标志物。它们还可能支持疫苗开发或作为抗病毒基因治疗的工具。尽管前景广阔,但挑战依然存在,如优化体外合成、改进递送方式(如脂质纳米颗粒)以及最小化免疫原性和脱靶效应。持续的研究对于完善递送方法并在临床模型中验证基于circRNA的策略至关重要。

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