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

Authors

• Ken Ichiro Matsunaga, A-Star, Institute of Bioengineering and Nanotechnology
• Michiko Kimoto, A-Star, Institute of Bioengineering and Nanotechnology
• Charlotte Hanson, National Cancer Institute at Frederick
• Michael Sanford, National Cancer Institute at Frederick
• Howard A. Young, National Cancer InstituteFollow
• Ichiro Hirao, A-Star, Institute of Bioengineering and NanotechnologyFollow

Date of this Version

12-22-2015

Citation

Scientific Reports 5:18478 (2015)

DOI: 10.1038/srep18478

Comments

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

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 (KD 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.