Rabiee Navid, Rabiee Mohammad
Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing 100084, China.
Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China.
ACS Pharmacol Transl Sci. 2025 Mar 12;8(4):1028-1049. doi: 10.1021/acsptsci.5c00047. eCollection 2025 Apr 11.
The development of precise and efficient delivery systems is pivotal for advancing CRISPR/Cas9 gene-editing technologies, particularly for therapeutic applications. Engineered metal-organic frameworks (MOFs) have emerged as a promising class of inorganic nonviral vectors, offering unique advantages such as tunable porosity, high cargo-loading capacity, and biocompatibility. This review explores the design and application of MOF-based nanoplatforms tailored for the targeted delivery of CRISPR/Cas9 components, aiming to enhance gene-editing precision and efficiency. By incorporating stimuli-responsive linkers and bioactive ligands, these MOFs enable controlled release of CRISPR/Cas9 payloads at the target site. Comparative discussions demonstrate superior performance of MOFs over conventional nonviral systems in terms of stability, transfection efficiency, and reduced off-target effects. Additionally, the intracellular trafficking mechanisms and the therapeutic potential of these platforms in preclinical models are discussed. These findings highlight the transformative potential of MOF-based delivery systems in overcoming the challenges associated with gene-editing technologies, such as immunogenicity and cytotoxicity, paving the way for their application in precision medicine. This review provides a blueprint for the integration of nanotechnology and genome editing, advancing the frontier of nonviral therapeutic delivery systems.
开发精确高效的递送系统对于推进CRISPR/Cas9基因编辑技术至关重要,特别是在治疗应用方面。工程化金属有机框架(MOF)已成为一类有前景的无机非病毒载体,具有诸如可调节孔隙率、高载药量和生物相容性等独特优势。本文综述探讨了为CRISPR/Cas9组件靶向递送量身定制的基于MOF的纳米平台的设计与应用,旨在提高基因编辑的精度和效率。通过结合刺激响应性连接体和生物活性配体,这些MOF能够在靶位点实现CRISPR/Cas9有效载荷的可控释放。对比讨论表明,在稳定性、转染效率和减少脱靶效应方面,MOF优于传统非病毒系统。此外,还讨论了这些平台在临床前模型中的细胞内运输机制和治疗潜力。这些发现凸显了基于MOF的递送系统在克服与基因编辑技术相关的挑战(如免疫原性和细胞毒性)方面的变革潜力,为其在精准医学中的应用铺平了道路。本文综述为纳米技术与基因组编辑的整合提供了蓝图,推动了非病毒治疗递送系统的前沿发展。
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