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- W2904329103 abstract "Accurate and efficient delivery of genome editing plasmids to targeted cells is of critical importance in genome editing. Herein, we prepared a multifunctional delivery vector with a combination of ligand-mediated selectivity and peptide-mediated transmembrane function to effectively deliver plasmids to targeted cancerous cells. In the delivery system, the clustered regularly interspaced short palindromic repeat-associated Cas9 nuclease (CRISPR-Cas9) plasmid is combined with protamine with membrane and nuclear translocating activities and co-precipitated with CaCO3, which is further decorated by AS1411-functionalized carboxymethyl chitosan and cell penetrating peptide (TAT)-functionalized carboxymethyl chitosan. The AS1411-mediated tumor cell/nuclear targeting and TAT-induced enhanced endocytosis result in obviously increased cellular uptake and nuclear transport. As a result, the CRISPR-Cas9 plasmid can be efficiently delivered to cancer cell nuclei to mediate genome editing, resulting in an efficacious knockout of CTNNB1 gene encoding β-catenin. More importantly, downregulation of β-catenin could effectively prevent its enrichment in nuclei and then significantly downregulate the expression of proteins, such as vimentin, Snail, MMP-2, MMP-9, CD44, Nanog, and Oct4 to prevent tumor progression and metastasis. The edited cancerous cells exhibit favorable remodulated properties including inhibited growth, suppressed migration and invasion, and reduced cancer stemness." @default.
- W2904329103 created "2018-12-22" @default.
- W2904329103 creator A5023500890 @default.
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- W2904329103 date "2018-12-12" @default.
- W2904329103 modified "2023-10-15" @default.
- W2904329103 title "Multifunctional Vector for Delivery of Genome Editing Plasmid Targeting β-Catenin to Remodulate Cancer Cell Properties" @default.
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- W2904329103 doi "https://doi.org/10.1021/acsami.8b17481" @default.
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