延边大学药学院,吉林延吉,133002;
摘要:成簇规律间隔短回文重复序列(CRISPR)/成簇规律间隔短回文重复序列相关蛋白(Cas)13技术是一种新兴的核糖核酸(RNA)编辑工具,因其高特异性和灵活性,在基因功能研究和疾病治疗领域展现出巨大潜力。然而,递送问题仍是限制CRISPR/Cas13系统走向临床的主要障碍。本文全面综述了CRISPR/Cas13递送系统的现有优化策略,涵盖病毒载体工程化改造、脂质体递送技术突破及新型非病毒递送体系开发。此外,本文还讨论了其在遗传疾病治疗、抗病毒免疫增强等医学领域的应用潜力。最后,本文展望了CRISPR/Cas13递送系统的未来发展方向和前景,为开发新一代CRISPR/Cas递送系统提供理论支撑和参考。
关键词:成簇规律间隔短回文重复序列;成簇规律间隔短回文重复序列相关蛋白;递送系统;优化策略;临床应用
参考文献
[1]VAN DER OOST J, WESTRA E R, JACKSON R N, et al. Unravelling the structural and mechanistic basis of CRISPR-Cas systems [J]. Nat Rev Microbiol, 2014, 12(7): 479-92.
[2]JIANG F, DOUDNA J A. CRISPR-Cas9 Structures and Mechanisms [J]. Annu Rev Biophys, 2017, 46: 505-29.
[3]HAMILTON J R, CHEN E, PEREZ B S, et al. In vivo human T cell engineering with enveloped delivery vehicles [J]. Nat Biotechnol, 2024, 42(11): 1684-92.
[4]MUSUNURU K, CHADWICK A C, MIZOGUCHI T, et al. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates [J]. Nature, 2021, 593(7859): 429-34.
[5]WU Z, ZHAO C, AI H, et al. A Susceptible Cell-Selective Delivery (SCSD) of mRNA-Encoded Cas13d Against Influenza Infection [J]. Adv Sci (Weinh), 2025, 12(9): e2414651.
[6]FREIJE C A, MYHRVOLD C, BOEHM C K, et al. Programmable Inhibition and Detection of RNA Viruses Using Cas13 [J]. Mol Cell, 2019, 76(5): 826-37.e11.