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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.

Lipid nanoparticle-mediated efficient delivery of CRISPR/Cas9 for tumor therapy