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Lipid nanoparticle-mediated efficient delivery of CRISPR/Cas9 for tumor therapy
NPG Asia Materials ( IF 8.6 ) Pub Date : 2017-10-27 , DOI: 10.1038/am.2017.185
Lingmin Zhang , Peng Wang , Qiang Feng , Nuoxin Wang , Zitian Chen , Yanyi Huang , Wenfu Zheng , Xingyu Jiang

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.



中文翻译:

脂质纳米颗粒介导的CRISPR / Cas9高效递送用于肿瘤治疗

新兴的CRISPR / Cas9系统代表了一个有前途的基因组编辑平台。然而,其低转染效率是阻碍CRISPR / Cas9基因编辑潜力的应用的主要问题。在此,我们通过筛选超过56种试剂的库,构建了一种新型的基于聚乙二醇磷脂修饰的阳离子脂质纳米颗粒(PLNP)的递送系统,该系统可以浓缩和封装Cas9 /单向导RNA(sgRNA)质粒( DNA)形成核-壳结构(PLNP / DNA),可在体外介导A375细胞成功将Cas9 / sgPLK-1质粒成功转染达47.4%。的瘤内注射Cas9 / sgPLK-1质粒的成黑色素瘤荷瘤小鼠导致的显著下调Polo样激酶1(PLK-1)的肿瘤生长的蛋白质和抑制(> 67%)在体内。这种方法提供了可用于具有高效率和安全性都递送CRISPR / Cas9系统的通用方法在体外体内

更新日期:2018-06-03
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