State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, University College London, London WC1N 1AX, UK.
Nat Commun. 2016 Nov 24;7:13580. doi: 10.1038/ncomms13580.
The efficient and precise delivery of siRNA to target cells is critical to successful gene therapy. While novel nanomaterials enhance delivery efficiency, it still remains challenging for precise gene delivery to overcome nonspecific adsorption and off-target effect. Here we design a dual lock-and-key system to perform cell-subtype-specific recognition and siRNA delivery. The siRNA 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 'dual locks' sequentially, which leads to cell-subtype discrimination and precise siRNA delivery for high efficient gene silencing. The success of this strategy demonstrates the precise delivery of siRNA to specific target cells by controlling multiple parameters, thus paving the way for application of RNAi in accurate diagnosis and intervention.
将 siRNA 高效且精确地递送到靶细胞对于成功的基因治疗至关重要。虽然新型纳米材料提高了递送效率，但精确的基因递送仍然难以克服非特异性吸附和脱靶效应。在这里，我们设计了一种双重锁钥系统来进行细胞亚型特异性识别和 siRNA 递 送。siRNA 自组装在经过发夹结构修饰的寡核苷酸纳米载体中，该结构既充当“智能钥匙”又充当递送载体。自动切割的发夹结构可以通过与两个适体作为“双重锁”依次反应在靶细胞膜上原位激活，从而实现细胞亚型的区分和精确的 siRNA 递 送，以实现高效的基因沉默。该策略的成功表明通过控制多个参数可将 siRNA 精确递送到特定的靶细胞，从而为 RNAi 在精确诊断和干预中的应用铺平了道路。
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