Issue 1, 2018

Caged circular siRNAs for photomodulation of gene expression in cells and mice

Abstract

By means of RNA interference (RNAi), small interfering RNAs (siRNAs) play important roles in gene function study and drug development. Recently, photolabile siRNAs were developed to elucidate the process of gene silencing in terms of space, time and degree through chemical modification of siRNAs. We report herein a novel type of photolabile siRNA that was synthesized through cyclizing two ends of a single stranded RNA with a photocleavable linker. These circular siRNAs became more resistant to serum degradation. Using reporter assays of firefly/Renilla luciferase and GFP/RFP, the gene silencing activities of caged circular siRNAs for both genes were evaluated in HEK293 cells. The results indicated that the target genes were successfully photomodulated using these caged circular siRNAs that were formed by caged circular antisense guide RNAs and their linear complementary sense RNAs. Using the caged circular siRNA targeting GFP, we also successfully achieved photomodulation of GFP expression in mice. Upon further optimization, this new type of caged circular siRNA is expected to be a promising tool for studying gene therapy.

Graphical abstract: Caged circular siRNAs for photomodulation of gene expression in cells and mice

Supplementary files

Article information

Article type
Edge Article
Submitted
02 Sep 2017
Accepted
18 Oct 2017
First published
19 Oct 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2018,9, 44-51

Caged circular siRNAs for photomodulation of gene expression in cells and mice

L. Zhang, D. Liang, Y. Wang, D. Li, J. Zhang, L. Wu, M. Feng, F. Yi, L. Xu, L. Lei, Q. Du and X. Tang, Chem. Sci., 2018, 9, 44 DOI: 10.1039/C7SC03842A

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