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
Descripción
Sumario: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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