Department of Urology, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Department of Pathology, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Medical Research Institute, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China.
Adv Drug Deliv Rev. 2021 Jan;168:246-258. doi: 10.1016/j.addr.2020.10.014. Epub 2020 Oct 27.
The discovery and applications of clustered regularly interspaced short palindromic repeat (CRISPR) systems have revolutionized our ability to track and manipulate specific nucleic acid sequences in many cell types of various organisms. The robustness and simplicity of these platforms have rapidly extended their applications from basic research to the development of therapeutics. However, many hurdles remain on the path to translation of the CRISPR systems to therapeutic applications: efficient delivery, detectable off-target effects, potential immunogenicity, and others. Chemical modifications provide a variety of protection options for guide RNA, Cas9 mRNA and donor templates. For example, chemically modified gRNA demonstrated enhanced on-target editing efficiency, minimized immune response and decreased off-target genome editing. In this review, we summarize the use of chemically modified nucleotides for CRISPR-mediated genome editing and emphasize open questions that remain to be addressed in clinical applications.
CRISPR 系统的发现和应用彻底改变了我们在多种生物体的多种细胞类型中跟踪和操纵特定核酸序列的能力。这些平台的强大功能和简单性迅速将其应用从基础研究扩展到治疗药物的开发。然而，将 CRISPR 系统转化为治疗应用仍然存在许多障碍：有效的递送、可检测的脱靶效应、潜在的免疫原性等。化学修饰为向导 RNA、Cas9 mRNA 和供体模板提供了多种保护选项。例如，化学修饰的 gRNA 表现出增强的靶编辑效率、最小化的免疫反应和减少的脱靶基因组编辑。在这篇综述中，我们总结了化学修饰核苷酸在 CRISPR 介导的基因组编辑中的应用，并强调了在临床应用中仍需解决的问题。
