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• W2765484860 abstract "The emerging CRISPR/Cas9 system represents a promising platform for genome editing. However, its low transfection efficiency is a major problem hampering the application of the gene-editing potential of CRISPR/Cas9. Herein, by screening a pool of more than 56 kinds of agents, we constructed a novel polyethylene glycol phospholipid-modified cationic lipid nanoparticle (PLNP)-based delivery system that can condense and encapsulate a Cas9/single-guide RNA (sgRNA) plasmid (DNA) to form a core–shell structure (PLNP/DNA) that mediated up to 47.4% successful transfection of Cas9/sgPLK-1 plasmids in A375 cells in vitro. An intratumor injection of Cas9/sgPLK-1 plasmids into melanoma tumor-bearing mice resulted in significant downregulation of Polo-like kinase 1 (PLK-1) protein and suppression of the tumor growth (>67%) in vivo. This approach provides a versatile method that could be used for delivering the CRISPR/Cas9 system with high efficiency and safety both in vitro and in vivo. A material for delivering CRISPR–Cas9 to the nuclei of cells has been developed by researchers in China. CRISPR–Cas9 is a powerful gene editing system found in bacteria. Scientists have recently harnessed it to edit genes in mammalian cells and even human embryos, opening the door to a host of revolutionary medical treatments. But the plasmid encoding CRISPR–Cas9 is a large nucleic acid, which limits the efficiency with which it can enter target cells. Now, Xingyu Jiang from the National Center for Nanoscience and Technology, Beijing, and colleagues have demonstrated a versatile method for delivering CRISPR–Cas9 efficiently and safely. After screening more than 56 agents, they constructed polyethylene glycol phospholipid–modified cationic lipid nanoparticles to encapsulate CRISPR–Cas9, which allowed nanoparticles to be delivered to melanoma cells with an efficiency of 47%. Our work contributes to synthesize a vehicle based on lipid nanoparticles, which can effectively deliver Cas9/sgRNA-fused plasmid DNA in vitro and in vivo. This approach mediated successful transfection of Cas9/sgRNA plasmids in multiple cell lines in vitro. The vehicle carrying Cas9/sgRNA targeting PLK-1 resulted in significant down-regulation of PLK-1 protein and suppression of melanoma growth in vivo." @default.
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• W2765484860 date "2017-10-01" @default.
• W2765484860 modified "2023-10-16" @default.
• W2765484860 title "Lipid nanoparticle-mediated efficient delivery of CRISPR/Cas9 for tumor therapy" @default.
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• W2765484860 doi "https://doi.org/10.1038/am.2017.185" @default.
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