Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications

We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by...

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Detalles Bibliográficos
Autores principales: Matsunaga, Ken-ichiro, Kimoto, Michiko, Hanson, Charlotte, Sanford, Michael, Young, Howard A., Hirao, Ichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686876/
https://www.ncbi.nlm.nih.gov/pubmed/26690672
http://dx.doi.org/10.1038/srep18478
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author Matsunaga, Ken-ichiro
Kimoto, Michiko
Hanson, Charlotte
Sanford, Michael
Young, Howard A.
Hirao, Ichiro
author_facet Matsunaga, Ken-ichiro
Kimoto, Michiko
Hanson, Charlotte
Sanford, Michael
Young, Howard A.
Hirao, Ichiro
author_sort Matsunaga, Ken-ichiro
collection PubMed
description We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing their high affinity. By this method, >80% of the remodeled DNA aptamer targeting interferon-γ (K(D) of 33 pM) survived in human serum at 37 °C after 3 days under our experimental conditions, and sustainably inhibited the biological activity of interferon-γ.
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spelling pubmed-46868762015-12-31 Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications Matsunaga, Ken-ichiro Kimoto, Michiko Hanson, Charlotte Sanford, Michael Young, Howard A. Hirao, Ichiro Sci Rep Article We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing their high affinity. By this method, >80% of the remodeled DNA aptamer targeting interferon-γ (K(D) of 33 pM) survived in human serum at 37 °C after 3 days under our experimental conditions, and sustainably inhibited the biological activity of interferon-γ. Nature Publishing Group 2015-12-22 /pmc/articles/PMC4686876/ /pubmed/26690672 http://dx.doi.org/10.1038/srep18478 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Matsunaga, Ken-ichiro
Kimoto, Michiko
Hanson, Charlotte
Sanford, Michael
Young, Howard A.
Hirao, Ichiro
Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications
title Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications
title_full Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications
title_fullStr Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications
title_full_unstemmed Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications
title_short Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications
title_sort architecture of high-affinity unnatural-base dna aptamers toward pharmaceutical applications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686876/
https://www.ncbi.nlm.nih.gov/pubmed/26690672
http://dx.doi.org/10.1038/srep18478
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