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基于脂质、无机、聚合物和 DNA 的纳米载体用于递送 CRISPR/Cas9 系统。

Lipid-, Inorganic-, Polymer-, and DNA-Based Nanocarriers for Delivery of the CRISPR/Cas9 system.

机构信息

Frontiers Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), Institute of Biomolecular and Biomedical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, P. R. China.

出版信息

Chembiochem. 2023 Aug 15;24(16):e202300180. doi: 10.1002/cbic.202300180. Epub 2023 Jul 25.

Abstract

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (CRISPR/Cas9) system has been widely explored for the precise manipulation of target DNA and has enabled efficient genomic editing in cells. Recently, CRISPR/Cas9 has shown promising potential in biomedical applications, including disease treatment, transcriptional regulation and genome-wide screening. Despite these exciting achievements, efficient and controlled delivery of the CRISPR/Cas9 system has remained a critical obstacle to its further application. Herein, we elaborate on the three delivery forms of the CRISPR/Cas9 system, and discuss the composition, advantages and limitations of these forms. Then we provide a comprehensive overview of the carriers of the system, and focus on the nonviral nanocarriers in chemical methods that facilitate efficient and controlled delivery of the CRISPR/Cas9 system. Finally, we discuss the challenges and prospects of the delivery methods of the CRISPR/Cas9 system in depth, and propose strategies to address the intracellular and extracellular barriers to delivery in clinical applications.

摘要

簇状规律间隔短回文重复序列 (CRISPR)/相关蛋白 9 (CRISPR/Cas9) 系统已被广泛用于精确操作靶 DNA,并实现了细胞内的高效基因组编辑。最近,CRISPR/Cas9 在生物医学应用中显示出了有前景的潜力,包括疾病治疗、转录调控和全基因组筛选。尽管取得了这些令人兴奋的成就,但 CRISPR/Cas9 系统的有效和可控传递仍然是其进一步应用的关键障碍。本文详细阐述了 CRISPR/Cas9 系统的三种传递形式,并讨论了这些形式的组成、优点和局限性。然后,我们对该系统的载体进行了全面概述,并重点介绍了化学方法中非病毒纳米载体在促进 CRISPR/Cas9 系统有效和可控传递方面的作用。最后,我们深入讨论了 CRISPR/Cas9 系统传递方法的挑战和前景,并提出了在临床应用中解决细胞内和细胞外传递障碍的策略。

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