Ren, K;
Zhang, Y;
Zhang, X;
Liu, Y;
Yang, M;
Ju, H;
(2018)
In Situ SiRNA Assembly in Living Cells for Gene Therapy with MicroRNA Triggered Cascade Reactions Templated by Nucleic Acids.
ACS Nano
, 12
(11)
pp. 10797-10806.
10.1021/acsnano.8b02403.
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Abstract
The in situ generation of siRNAs in living cells can greatly enhance the specificity and efficiency of gene therapy. Inspired by the natural molecular machines that organize different compartments sequentially in a limited space to facilitate cellular process, this work constructs a DNA nanomachine (DNM) by alternately hybridizing two pairs of DNA/RNA hybrids to a DNA scaffold generated by rolling circle amplification for highly efficient in situ siRNA assembly in living cells. After target cell-specific delivery of DNM, intracellular specific microRNA can work as a trigger to operate the DNM by initiating DNA cascade displacement reaction between DNA/RNA hybrids along the scaffold for continuous generation of siRNAs. Using miR-21 as a model, efficient siRNAs generation is achieved via DNA templated cascade reaction, which demonstrated impressive suppressions to VEGF mRNA and protein expressions in cells and in vivo tumor growth and indicated promising application of the designed strategy in gene therapy.
Type: | Article |
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Title: | In Situ SiRNA Assembly in Living Cells for Gene Therapy with MicroRNA Triggered Cascade Reactions Templated by Nucleic Acids |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1021/acsnano.8b02403 |
Publisher version: | https://doi.org/10.1021/acsnano.8b02403 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | DNA nanomachine, DNA templated cascade reaction, gene interference, microRNA, siRNA generation |
UCL classification: | UCL 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/10063571 |
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