title: A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery.
abstract: 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.
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, University College London, London WC1N 1AX, UK.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
authors.forename: Huangxian
authors.initials: H
authors.lastname: Ju
mesh_terms: D052157:Aptamers, Nucleotide; D045744:Cell Line, Tumor; D004247:DNA; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D055029:Inverted Repeat Sequences; D049329:Nanostructures; D034741:RNA, Small Interfering; D000067492:RNAi Therapeutics / Q000379:methods*
chemical_list: D052157:Aptamers, Nucleotide; D034741:RNA, Small Interfering; D004247:DNA