Supramolecular Nanosubstrate-Mediated Delivery for CRISPR/Cas9 Gene Disruption and Deletion

文献类型： 外文期刊

第一作者： Ban, Qian

作者： Ban, Qian;Qiao, Li;Xia, Haidong;Yang, Peng;Xue, Jingjing;Sun, Na;Zhang, Ryan Y.;Zhang, Ceng;Lee, Athena;Antovski, Petar;Zhang, Xinyue;Tseng, Hsian-Rong;Chou, Shih-Jie;Lin, Ting-Yi;Ko, Yu-Ling;Chiou, Shih-Hwa;Chou, Shih-Jie;Lin, Ting-Yi;Ko, Yu-Ling;Chiou, Shih-Hwa;Wang, Fang;Xu, Xiaobin;Liu, Wenfei;Weiss, Paul S.;Xu, Xiaobin;Lee, Chin-Fa;Hui, Wenqiao;Liu, Dahai;Jonas, Steven J.

作者机构：

关键词： CRISPR; Cas9; Duchenne muscular dystrophy; gene editing; nanosubstrate-mediated delivery; supramolecular nanoparticles

期刊名称：SMALL （ 影响因子：13.281； 五年影响因子：12.463 ）

ISSN： 1613-6810

年卷期： 2021 年 17 卷 28 期

页码：

收录情况： SCI

摘要： The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) is an efficient and precise gene-editing technology that offers a versatile solution for establishing treatments directed at genetic diseases. Currently, CRISPR/Cas9 delivery into cells relies primarily on viral vectors, which suffer from limitations in packaging capacity and safety concerns. These issues with a nonviral delivery strategy are addressed, where Cas9 center dot sgRNA ribonucleoprotein (RNP) complexes can be encapsulated into supramolecular nanoparticles (SMNP) to form RNP subset of SMNPs, which can then be delivered into targeted cells via supramolecular nanosubstrate-mediated delivery. Utilizing the U87 glioblastoma cell line as a model system, a variety of parameters for cellular-uptake of the RNP-laden nanoparticles are examined. Dose- and time-dependent CRISPR/Cas9-mediated gene disruption is further examined in a green fluorescent protein (GFP)-expressing U87 cell line (GFP-U87). The utility of an optimized SMNP formulation in co-delivering Cas9 protein and two sgRNAs that target deletion of exons 45-55 (708 kb) of the dystrophin gene is demonstrated. Mutations in this region lead to Duchenne muscular dystrophy, a severe genetic muscle wasting disease. Efficient delivery of these gene deletion cargoes is observed in a human cardiomyocyte cell line (AC16), induced pluripotent stem cells, and mesenchymal stem cells.

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