【作者】 刘颖； 任克维； 吴洁； 张玥； 朱靖； 鞠熀先；

【Author】 Ying Liu;K Ren;H Ju;Department of Chemistry, Nanjing University;

【机构】 南京大学化学化工学院生命分析化学国家重点实验室；

【摘要】 高效率和高选择性的siRNA靶向递运是基因治疗成功实施的关键。基于新型纳米结构的载运材料可以有效提高siRNA负载量与递运效率,然而有效避免非特异性吸附与"脱靶效应"的细胞亚型特异性精准siRNA递运仍是具有挑战性的问题。本文通过滚环扩增反应与DNA自组装合成了DNA纳米管负载VEGF siRNA,结合淋巴母细胞性白血病细胞（CEM）表面特异性核酸适体sgc8c,sgc4f^[1],实现了高特异性的CEM细胞精准识别与基因载运。DNA纳米管一端的发卡结构与sgc4f反应被激活变形,继而与sgc8c反应进入细胞,这一顺序反应"双开关"精准控制了"智能钥匙"DNA纳米管在CEM细胞表面的原位响应,极大提高了VEGF siRNA基因载运的选择性与特异性,以及CEM细胞内VEGF基因沉默和蛋白表达抑制效率。更多还原

【Abstract】 The efficient and precise delivery of siR NA to target cells is critical to the successful gene therapy. While novel nanomaterials enhance delivery efficiency, it still remains challenging for the precise gene delivery to overcome nonspecific adsorption and off-target effect. Here we design a "double locks-smart key" system to perform cell-subtype specific recognition and siR NA delivery. The siR NA is self-assembled in an oligonucleotide nano vehicle that is modified with a hairpin structure to act as both the "smart-key" and the delivery carrier. The auto-cleavable hairpin structure can be activated on site at target cell membrane by reacting with two aptamers as "double locks" sequentially, which leads to cell-subtype discrimination and precise siR NA delivery for high efficient gene silencing. The success of this strategy demonstrates the precise delivery of siR NA to specific target cells by controlling multiple parameters, thus paves the way for application of RNAi in accurate diagnosis and intervention.更多还原