Wang Peng, Zhang Lingmin, Xie Yangzhouyun, Wang Nuoxin, Tang Rongbing, Zheng Wenfu, Jiang Xingyu
Beijing Engineering Research Center for Bio Nanotechnology CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nano Science and Technology Beijing 100190 China.
College of Materials Science and Opto-Electronic Technology/Sino-Danish CollegeUniversity of Chinese Academy of Sciences Beijing 100049 China.
Adv Sci (Weinh). 2017 Sep 7;4(11):1700175. doi: 10.1002/advs.201700175. eCollection 2017 Nov.
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 () 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.
II型细菌成簇规律间隔短回文重复序列（CRISPR）-Cas9（CRISPR相关蛋白）系统是一种强大的基因编辑工具，但将CRISPR-Cas9非病毒递送至细胞或组织仍然是一个关键挑战。本文报道了一种通过具有金纳米簇（GNs）核心和脂质外壳的纳米载体递送Cas9蛋白和单向导RNA（sgRNA）质粒的策略。通过用HIV-1转录激活因子肽修饰GNs，货物（Cas9/sgRNA）可被递送至细胞核。该策略通过设计靶向肿瘤（）的sgRNA来治疗黑色素瘤。纳米颗粒（聚乙二醇-脂质/GNs/Cas9蛋白/sgPlk1质粒，LGCP）在体外使A375细胞的Plk1蛋白表达下调>70%。此外，LGCP在小鼠上使黑色素瘤进展抑制75%。因此，该策略可递送蛋白质-核酸杂交剂用于基因治疗。
