biostudies-literatureChen SChina Scholarship CouncilEuropean Research CouncilAlexander von Humboldt-Stiftung6604-6619https://www.ebi.ac.uk/biostudies/studies/S-EPMC11751667biostudies-literatureUnknown17(11)CRISPR-Cas9 has emerged as a highly effective and customizable genome editing tool, holding significant promise for the treatment of KRAS mutations in lung cancer. In this study, we introduce a novel micelleplex, named C14-PEI, designed to co-deliver Cas9 mRNA and sgRNA efficiently to excise the mutated KRAS allele in lung cancer cells. C14-PEI is synthesised from 1,2-epoxytetradecane and branched PEI 600 Da <i>via</i> a ring-opening reaction. The resulting C14-PEI has a critical micelle concentration (CMC) of approximately 20.86 ± 0.15 mg L^-1, indicating its ability to form stable micelles at low concentrations. C14-PEI efficiently encapsulates mRNA into micelleplexes through electrostatic interactions. When the mass ratio is 8 (w/w 8), the C14-PEI formulation exhibits conducivNanoscaleA novel micelleplex for tumour-targeted delivery of CRISPR-Cas9 against KRAS-mutated lung cancer.PMC11751667637830ERC-2014-StG-637830Pinto Carneiro STriki MChen SMerkel OMfalseA novel micelleplex for tumour-targeted delivery of CRISPR-Cas9 against KRAS-mutated lung cancer.CRISPR-Cas9 has emerged as a highly effective and customizable genome editing tool, holding significant promise for the treatment of KRAS mutations in lung cancer. In this study, we introduce a novel micelleplex, named C14-PEI, designed to co-deliver Cas9 mRNA and sgRNA efficiently to excise the mutated KRAS allele in lung cancer cells. C14-PEI is synthesised from 1,2-epoxytetradecane and branched PEI 600 Da <i>via</i> a ring-opening reaction. The resulting C14-PEI has a critical micelle concentration (CMC) of approximately 20.86 ± 0.15 mg L^-1, indicating its ability to form stable micelles at low concentrations. C14-PEI efficiently encapsulates mRNA into micelleplexes through electrostatic interactions. When the mass ratio is 8 (w/w 8), the C14-PEI formulation exhibits conduciv2025-01-01T00:00:00Z2025 Mar2025-04-04T01:41:21.161Z2025-04-04T01:41:21.161ZS-EPMC117516673983878010.1039/d4nr03471f