Issue 4, 2017

Nuclear-targeted siRNA delivery for long-term gene silencing

Abstract

Developing effective nonviral siRNA delivery systems for long-term gene silencing remains a great challenge. Here we present a nuclear-targeted siRNA delivery system that can induce long-term gene silencing in cancer cells. The nanocarrier consists of gold nanoparticles modified with a dense shell of synthetic siRNAs and nuclear localization signal (NLS) peptides. The NLS peptide could translocate the nanocarrier into the nucleus and the siRNA was designed to target the promoter of thymidine kinase 1 and trigger the RNA-directed DNA methylation, thereby enabling the nuclear-targeted gene silencing. Compared with traditional gene silencing in cytoplasm, long-lasting gene knockdown could be achieved for the nuclear-targeted nanocarrier, which lasts for more than 30 days. The long-term gene silencing induced by nuclear-targeted siRNA delivery could effectively inhibit the proliferation of cancer cells and prevent the formation of a tumor in a mouse model.

Graphical abstract: Nuclear-targeted siRNA delivery for long-term gene silencing

Supplementary files

Article information

Article type
Edge Article
Submitted
26 sept. 2016
Accepted
19 janv. 2017
First published
19 janv. 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 license

Chem. Sci., 2017,8, 2816-2822

Nuclear-targeted siRNA delivery for long-term gene silencing

N. Li, H. Yang, Z. Yu, Y. Li, W. Pan, H. Wang and B. Tang, Chem. Sci., 2017, 8, 2816 DOI: 10.1039/C6SC04293G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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