Engineered Metal–Organic Frameworks for Targeted CRISPR/Cas9 Gene Editing

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.