Genome Editing for Cancer Therapy: Delivery of Cas9 Protein/sgRNA Plasmid via a Gold Nanocluster/Lipid Core-Shell Nanocarrier
Genome Editing for Cancer Therapy: Delivery of Cas9 Protein/sgRNA Plasmid via a Gold Nanocluster/Lipid Core-Shell Nanocarrier
复制标题
用于癌症治疗的基因组编辑：通过金纳米簇/脂质核壳纳米载体递送 Cas9 蛋白/sgRNA 质粒
DOI：
10.1002/advs.201700175
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发表时间：
2017-11-01
期刊：
影响因子：
15.1
通讯作者：
Jiang, Xingyu
中科院分区：
文献类型：
--
作者：
Wang, Peng;Zhang, Lingmin;Jiang, Xingyu
II型细菌聚集，有规律地间隔，短回传重复(CRISPR)-Cas9 （CRISPR相关蛋白）系统（CRISPR-Cas9）是基因编辑的强大工具箱，然而，将CRISPR-Cas9非病毒传递到细胞或组织仍然是一个关键挑战。本文报道了一种以金纳米团簇（GNs）为核心、脂质为外壳的纳米载体递送Cas9蛋白和单导RNA （sgRNA）质粒的策略。通过用hiv -1转录肽反激活子修饰GNs，将Cas9/sgRNA转运到细胞核中。通过设计靶向肿瘤的polo样激酶-1 （Plk1）的sgRNA，该策略被用于治疗黑色素瘤。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Plk1蛋白表达下调约70%。此外，LGCP对小鼠黑色素瘤的抑制率为75%。因此，这种策略可以为基因治疗提供蛋白质-核酸混合剂。
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.