Issue 22, 2017

Enhancement of synergistic gene silencing by RNA interference using branched “3-in-1” trimer siRNA

Abstract

Nanostructured RNA carrying three different siRNAs was assembled to silence three target genes (Axin, APC, and GSK-3β) in the Wnt/β-catenin signaling pathway. The trimer RNA nanostructure included equimolar concentrations of three oligonucleotide sequences. The three armed structures and the size of the trimer RNA were confirmed by agarose gel electrophoresis, atomic force microscopy, and dynamic light scattering. In the presence of 10% human serum, the trimer RNA was able to resist degradation and maintained an intact structure for more than two hours. Protein expression analyses showed specific repression of the target proteins by siRNAs. As a result, the expression of luciferase in a β-catenin reporter vector was significantly increased by the trimer RNA compared with a pool of the three individual siRNAs. This high activity at a low concentration was considered to be due to the 3-in-1 format of the trimer and the long-term resistance to serum proteins by nanostructure formation. We demonstrated that a nanostructured “3-in-1” siRNA is effective in enhancing the effect of RNA interference.

Graphical abstract: Enhancement of synergistic gene silencing by RNA interference using branched “3-in-1” trimer siRNA

Supplementary files

Article information

Article type
Paper
Submitted
28 מרץ 2017
Accepted
24 אפר 2017
First published
18 מאי 2017

J. Mater. Chem. B, 2017,5, 4044-4051

Enhancement of synergistic gene silencing by RNA interference using branched “3-in-1” trimer siRNA

B. G. Nair, Y. Zhou, K. Hagiwara, M. Ueki, T. Isoshima, H. Abe and Y. Ito, J. Mater. Chem. B, 2017, 5, 4044 DOI: 10.1039/C7TB00846E

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