School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Key Laboratory of Electrical Insulation and Thermal Ageing, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
Department of Paediatric Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200092, China.
Nanoscale. 2019 Oct 7;11(37):17211-17215. doi: 10.1039/c9nr05233j. Epub 2019 Sep 18.
Herein, we report a non-cationic DNA-crosslinked nanogel for intracellular delivery of a Cas9 and single guide RNA (Cas9/sgRNA) complex. A DNA-grafted polycaprolactone brush (DNA-g-PCL) is first loaded with the Cas9/sgRNA complex and then crosslinked by DNA linkers via nucleic acid hybridization to form a nanosized hydrogel, in which the gene editing tools are embedded and protected inside. With compact architecture, the Cas9/sgRNA complex-containing nanogel exhibited excellent physiological stability against nuclease digestion and enhanced cellular uptake efficiency, making the delivery system a promising tool for target genome editing.
在此,我们报告了一种非阳离子 DNA 交联纳米凝胶,用于细胞内递送 Cas9 和单指导 RNA(Cas9/sgRNA)复合物。首先将 Cas9/sgRNA 复合物加载到接枝有 DNA 的聚己内酯刷(DNA-g-PCL)上,然后通过 DNA 接头通过核酸杂交进行交联,形成纳米级水凝胶,其中嵌入并保护有基因编辑工具。含有 Cas9/sgRNA 复合物的纳米凝胶具有紧凑的结构,对核酸酶消化具有优异的生理稳定性和增强的细胞摄取效率,使该递送系统成为靶基因组编辑的有前途的工具。