The type II bacterial clustered, regularly interspaced, short palindromic repeats (CRISPR)‐Cas9 (CRISPR‐associated protein) system (CRISPR‐Cas9) is a powerful toolbox for gene‐editing, however, the nonviral delivery of CRISPR‐Cas9 to cells or tissues remains a key challenge. This paper reports a strategy to deliver Cas9 protein and single guide RNA (sgRNA) plasmid by a nanocarrier with a core of gold nanoclusters (GNs) and a shell of lipids. By modifying the GNs with HIV‐1‐transactivator of transcription peptide, the cargo (Cas9/sgRNA) can be delivered into cell nuclei. This strategy is utilized to treat melanoma by designing sgRNA targeting Polo‐like kinase‐1 (Plk1) of the tumor. The nanoparticle (polyethylene glycol‐lipid/GNs/Cas9 protein/sgPlk1 plasmid, LGCP) leads to >70% down‐regulation of Plk1 protein expression of A375 cells in vitro. Moreover, the LGCP suppresses melanoma progress by 75% on mice. Thus, this strategy can deliver protein‐nucleic acid hybrid agents for gene therapy.

中文翻译：

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癌症治疗的基因组编辑：通过金纳米簇/脂质核心-壳纳米载体递送Cas9蛋白/ sgRNA质粒

II型细菌簇状，规则间隔，短回文重复序列（CRISPR）-Cas9（CRISPR相关蛋白）系统（CRISPR-Cas9）是用于基因编辑的强大工具箱，但是，CRISPR-Cas9非病毒递送至细胞或组织仍然是关键的挑战。本文报道了一种通过具有金纳米簇（GNs）核心和脂质壳的纳米载体递送Cas9蛋白和单向导RNA（sgRNA）质粒的策略。通过用HIV-1反式转录激活因子修饰GN，可以将货物（Cas9 / sgRNA）传递到细胞核中。通过设计靶向Polo样激酶1（Plk1）的sgRNA，该策略可用于治疗黑色素瘤）的肿瘤。纳米颗粒（聚乙二醇-脂质/ GNs / Cas9蛋白/ sgPlk1质粒，LGCP）导致体外A375细胞的Plk1蛋白表达下调> 70％。此外，LGCP可抑制小鼠黑色素瘤进展75％。因此，这种策略可以为基因治疗提供蛋白质-核酸杂合剂。