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To overcome these concerns, herein we report a lipid\u2010silica hybrid nanoparticle platform for fusogenic association and secured transfection of CRISPR\/Cas9 (FAST\u2010CRISPR), designed for rapid cytosolic delivery of CRISPR\/Cas9 ribonucleoproteins, followed by efficient gene editing. Through direct fusion with the plasma membrane and bypassing conventional endocytic barriers, FAST\u2010CRISPR nanoparticles displayed superior intracellular delivery efficacy. Optimizing lipid compositions, we discovered that a 1:1 weight mixture of cationic DOTAP and ionizable DODMA lipids, combined with tailored large\u2010pore silica nanoparticles, enables enhanced loading capacity, rapid cytosolic dispersion, and significant nuclear transport of Cas9\/gRNA complexes. FAST\u2010CRISPR nanoparticles efficiently delivered multiplex genome\u2010targeting ribonucleoproteins to induce targeted double\u2010strand DNA breaks, triggering apoptosis in cancer cells and significantly suppressing tumor growth in a mouse xenograft model without systemic toxicity. Our findings demonstrate the therapeutic efficacy and translational potential of FAST\u2010CRISPR nanoparticles as a safe and versatile non\u2010viral delivery platform for precision genome editing.<\/jats:p>","DOI":"10.1002\/smll.202511362","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T14:27:52Z","timestamp":1768228072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["FAST\u2010CRISPR: Fusogenic Association and Secured Transfection of CRISPR\/Cas9 Ribonucleoproteins Using Lipid\u2010Silica Hybrid Nanoparticles for Therapeutic Genome Editing"],"prefix":"10.1002","volume":"22","author":[{"given":"Minjong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biological Science Ulsan National Institute of Science and Technology  Ulsan Republic of 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