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Life sciences · Journal article
Acs Nano · October 6, 2026
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Abstract As a powerful gene-editing tool, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system features simple construction, precise targeting, and higher editing efficiency, bringing prospects of radical cures for numerous critical illnesses at the genomic level. To date, ex vivo CRISPR/Cas-based gene therapies represented by Casgevy have achieved significant clinical advances. Nevertheless, cumbersome operational workflows and prohibitive treatment costs severely hinder their widespread clinical accessibility. In contrast, in vivo CRISPR/Cas-based gene therapies stand out with convenient administration procedures and reduced overall costs, endowing them with enormous translational potential. Although it holds great promise, the clinical translation of in vivo CRISPR/Cas-based gene therapies remains hampered by a number of factors. Among those multiple obstacles restricting the clinical translation of in vivo CRISPR/Cas-based gene therapies, delivery systems constitute the core bottleneck dominating in vivo editing efficiency and therapeutic potency. Centered on delivery platforms for in vivo CRISPR/Cas-based gene therapies, this review systematically summarizes prevailing in vivo CRISPR/Cas nano delivery systems, recapitulates relevant preclinical and clinical outcomes, discusses translational hurdles, and prospects the evolution of next-generation delivery systems, aiming to facilitate further development of in vivo CRISPR/Cas-based gene therapies.