Protecting microRNAs from RNase degradation with steric DNA nanostructures

Tumor suppressive microRNAs are potent molecules that might cure cancer, one day. Despite the many advanced strategies for delivery of these microRNAs to the cell, there are few therapeutic microRNAs in clinical use. Progress in microRNA bioapplications is hindered by a high vulnerability of exogene...

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Main Authors: Qian, H., Tay, Chor Yong, Setyawati, M. I., Chia, S. L., Lee, D. S., Leong, D. T.
Other Authors: School of Materials Science & Engineering
Format: Journal Article
Language:English
Published: 2018
Subjects:
Online Access:https://hdl.handle.net/10356/87261
http://hdl.handle.net/10220/44373
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author Qian, H.
Tay, Chor Yong
Setyawati, M. I.
Chia, S. L.
Lee, D. S.
Leong, D. T.
author2 School of Materials Science & Engineering
author_facet School of Materials Science & Engineering
Qian, H.
Tay, Chor Yong
Setyawati, M. I.
Chia, S. L.
Lee, D. S.
Leong, D. T.
author_sort Qian, H.
collection NTU
description Tumor suppressive microRNAs are potent molecules that might cure cancer, one day. Despite the many advanced strategies for delivery of these microRNAs to the cell, there are few therapeutic microRNAs in clinical use. Progress in microRNA bioapplications is hindered by a high vulnerability of exogeneous microRNA molecules to RNase degradation that occurs in extra- and intracellular physiological conditions. In this proof-of-concept study, we use a programmable self-assembled DNA nanostructure bearing a “shuriken” shape to not only deliver but more importantly protect a tumor suppressive microRNA-145 for a sufficiently long time to exert its therapeutic effect in human colorectal cancer cells. Our DNA nanostructure harbored complementary sequences that can hybridize with the microRNA cargo. This brings the microRNA–DNA duplex very close to the core structure such that the microRNA cargo becomes sterically shielded from RNase's degradative activity. Our novel DNA nanostructure based protector concept removes the degradative bottleneck that may plague other nucleic acid delivery strategies and presents a new paradigm towards exploiting these microRNAs for anti-cancer therapy.
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spelling ntu-10356/872612023-02-28T16:56:07Z Protecting microRNAs from RNase degradation with steric DNA nanostructures Qian, H. Tay, Chor Yong Setyawati, M. I. Chia, S. L. Lee, D. S. Leong, D. T. School of Materials Science & Engineering School of Biological Sciences DNA Nanostructures Tumor suppressive microRNAs are potent molecules that might cure cancer, one day. Despite the many advanced strategies for delivery of these microRNAs to the cell, there are few therapeutic microRNAs in clinical use. Progress in microRNA bioapplications is hindered by a high vulnerability of exogeneous microRNA molecules to RNase degradation that occurs in extra- and intracellular physiological conditions. In this proof-of-concept study, we use a programmable self-assembled DNA nanostructure bearing a “shuriken” shape to not only deliver but more importantly protect a tumor suppressive microRNA-145 for a sufficiently long time to exert its therapeutic effect in human colorectal cancer cells. Our DNA nanostructure harbored complementary sequences that can hybridize with the microRNA cargo. This brings the microRNA–DNA duplex very close to the core structure such that the microRNA cargo becomes sterically shielded from RNase's degradative activity. Our novel DNA nanostructure based protector concept removes the degradative bottleneck that may plague other nucleic acid delivery strategies and presents a new paradigm towards exploiting these microRNAs for anti-cancer therapy. Published version 2018-02-01T07:49:52Z 2019-12-06T16:38:25Z 2018-02-01T07:49:52Z 2019-12-06T16:38:25Z 2017 Journal Article Qian, H., Tay, C. Y., Setyawati, M. I., Chia, S. L., Lee, D. S., & Leong, D. T. (2017). Protecting microRNAs from RNase degradation with steric DNA nanostructures. Chemical Science, 8(2), 1062-1067. 2041-6520 https://hdl.handle.net/10356/87261 http://hdl.handle.net/10220/44373 10.1039/C6SC01829G en Chemical Science © 2017 The Author(s) (published by Royal Society of Chemistry). This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. 6 p. application/pdf
spellingShingle DNA
Nanostructures
Qian, H.
Tay, Chor Yong
Setyawati, M. I.
Chia, S. L.
Lee, D. S.
Leong, D. T.
Protecting microRNAs from RNase degradation with steric DNA nanostructures
title Protecting microRNAs from RNase degradation with steric DNA nanostructures
title_full Protecting microRNAs from RNase degradation with steric DNA nanostructures
title_fullStr Protecting microRNAs from RNase degradation with steric DNA nanostructures
title_full_unstemmed Protecting microRNAs from RNase degradation with steric DNA nanostructures
title_short Protecting microRNAs from RNase degradation with steric DNA nanostructures
title_sort protecting micrornas from rnase degradation with steric dna nanostructures
topic DNA
Nanostructures
url https://hdl.handle.net/10356/87261
http://hdl.handle.net/10220/44373
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