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用于靶向CRISPR/Cas9基因编辑的工程化金属有机框架

Engineered Metal-Organic Frameworks for Targeted CRISPR/Cas9 Gene Editing.

作者信息

Rabiee Navid, Rabiee Mohammad

机构信息

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.

出版信息

ACS Pharmacol Transl Sci. 2025 Mar 12;8(4):1028-1049. doi: 10.1021/acsptsci.5c00047. eCollection 2025 Apr 11.


DOI:10.1021/acsptsci.5c00047
PMID:40242591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11997888/
Abstract

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.

摘要

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。

相似文献

[1]
Engineered Metal-Organic Frameworks for Targeted CRISPR/Cas9 Gene Editing.

ACS Pharmacol Transl Sci. 2025-3-12

[2]
Unlocking the potential of CRISPR-Cas9 for cystic fibrosis: A systematic literature review.

Gene. 2025-3-20

[3]
Cell-Penetrating Peptides and CRISPR-Cas9: A Combined Strategy for Human Genetic Disease Therapy.

Hum Gene Ther. 2024-10

[4]
Advancing crop disease resistance through genome editing: a promising approach for enhancing agricultural production.

Front Genome Ed. 2024-6-26

[5]
Toxicity Challenges and Current Advancement in Metal-Organic Frameworks (MOFs) for Biomedical Applications.

Biol Trace Elem Res. 2025-6-24

[6]
Improving the use of CRISPR/Cas9 gene editing machinery as a cancer therapeutic tool with the help of nanomedicine.

3 Biotech. 2025-1

[7]
Flexible Metal-Organic Frameworks for Adsorptive Separation of Liquid Hydrocarbons.

Acc Chem Res. 2025-7-1

[8]
Multi-metal/ligand MOFs: Transformative materials for energy storage, photocatalysis, and sensor technologies.

Adv Colloid Interface Sci. 2025-7-1

[9]
Chemical Strategies to Modulate and Manipulate RNA Epigenetic Modifications.

Acc Chem Res. 2025-6-3

[10]
CRISPR/Cas9-mediated genome editing in Ganoderma lucidum: recent advances and biotechnological opportunities.

World J Microbiol Biotechnol. 2025-6-25

本文引用的文献

[1]
Computational Modeling of Reticular Materials: The Past, the Present, and the Future.

Adv Mater. 2024-12-26

[2]
Tailored Metal-Organic Framework-Based Nanozymes for Enhanced Enzyme-Like Catalysis.

Angew Chem Int Ed Engl. 2025-2-10

[3]
Letter: The risk-benefit balance of CRISPR-Cas screening systems in gene editing and targeted cancer therapy.

J Transl Med. 2024-11-7

[4]
Mechanism Exploration of the Photoelectrochemical Immunoassay for the Integration of Radical Generation with Self-Quenching.

Anal Chem. 2024-9-10

[5]
Osteoporosis: interferon-gamma-mediated bone remodeling in osteoimmunology.

Front Immunol. 2024

[6]
Advances in Receptor-Mediated, Tumor-Targeted Drug Delivery.

Adv Ther (Weinh). 2019-1

[7]
Emerging technology has a brilliant future: the CRISPR-Cas system for senescence, inflammation, and cartilage repair in osteoarthritis.

Cell Mol Biol Lett. 2024-5-2

[8]
Vanadium-doped metal-organic framework@ZnlnS core-shell heterojunction-attenuated photoelectrochemical immunoassay.

Talanta. 2024-8-1

[9]
Biologically produced and metal-organic framework delivered dual-cut CRISPR/Cas9 system for efficient gene editing and sensitized cancer therapy.

Acta Biomater. 2024-4-1

[10]
Breaking Osteoclast-Acid Vicious Cycle to Rescue Osteoporosis via an Acid Responsive Organic Framework-Based Neutralizing and Gene Editing Platform.

Small. 2024-5

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