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In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing

A computational and experimental integrated approach was applied in order to study the effect of engineering four DNA hairpins into an octahedral truncated DNA nanocage, to obtain a nanostructure able to recognize and bind specific oligonucleotide sequences. Modeling and classical molecular dynamics...

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Autores principales: Raniolo, Sofia, Iacovelli, Federico, Unida, Valeria, Desideri, Alessandro, Biocca, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981788/
https://www.ncbi.nlm.nih.gov/pubmed/31861821
http://dx.doi.org/10.3390/ijms21010061
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author Raniolo, Sofia
Iacovelli, Federico
Unida, Valeria
Desideri, Alessandro
Biocca, Silvia
author_facet Raniolo, Sofia
Iacovelli, Federico
Unida, Valeria
Desideri, Alessandro
Biocca, Silvia
author_sort Raniolo, Sofia
collection PubMed
description A computational and experimental integrated approach was applied in order to study the effect of engineering four DNA hairpins into an octahedral truncated DNA nanocage, to obtain a nanostructure able to recognize and bind specific oligonucleotide sequences. Modeling and classical molecular dynamics simulations show that the new H4-DNA nanocage maintains a stable conformation with the closed hairpins and, when bound to complementary oligonucleotides produces an opened conformation that is even more stable due to the larger hydrogen bond number between the hairpins and the oligonucleotides. The internal volume of the open conformation is much larger than the closed one, switching from 370 to 650 nm(3), and the predicted larger conformational change is experimentally detectable by gel electrophoresis. H4-DNA nanocages display high stability in serum, can efficiently enter the cells where they are stable and maintain the ability to bind, and sequester an intracellular-specific oligonucleotide. Moreover, H4-DNA nanocages, modified in order to recognize the oncogenic miR21, are able to seize miRNA molecules inside cells in a selective manner.
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spelling pubmed-69817882020-02-07 In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing Raniolo, Sofia Iacovelli, Federico Unida, Valeria Desideri, Alessandro Biocca, Silvia Int J Mol Sci Article A computational and experimental integrated approach was applied in order to study the effect of engineering four DNA hairpins into an octahedral truncated DNA nanocage, to obtain a nanostructure able to recognize and bind specific oligonucleotide sequences. Modeling and classical molecular dynamics simulations show that the new H4-DNA nanocage maintains a stable conformation with the closed hairpins and, when bound to complementary oligonucleotides produces an opened conformation that is even more stable due to the larger hydrogen bond number between the hairpins and the oligonucleotides. The internal volume of the open conformation is much larger than the closed one, switching from 370 to 650 nm(3), and the predicted larger conformational change is experimentally detectable by gel electrophoresis. H4-DNA nanocages display high stability in serum, can efficiently enter the cells where they are stable and maintain the ability to bind, and sequester an intracellular-specific oligonucleotide. Moreover, H4-DNA nanocages, modified in order to recognize the oncogenic miR21, are able to seize miRNA molecules inside cells in a selective manner. MDPI 2019-12-20 /pmc/articles/PMC6981788/ /pubmed/31861821 http://dx.doi.org/10.3390/ijms21010061 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Raniolo, Sofia
Iacovelli, Federico
Unida, Valeria
Desideri, Alessandro
Biocca, Silvia
In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing
title In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing
title_full In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing
title_fullStr In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing
title_full_unstemmed In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing
title_short In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing
title_sort in silico and in cell analysis of openable dna nanocages for mirna silencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981788/
https://www.ncbi.nlm.nih.gov/pubmed/31861821
http://dx.doi.org/10.3390/ijms21010061
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