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A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery

Ren, K; Liu, Y; Wu, J; Zhang, Y; Zhu, J; Yang, M; Ju, H; (2016) A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery. Nature Communications , 7 , Article 13580. 10.1038/ncomms13580. Green open access

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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.

Type: Article
Title: A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms13580
Publisher version: http://dx.doi.org/10.1038/ncomms13580
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Oligo delivery; RNA; Targeted therapies
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1531006
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