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

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-? (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-?.

SUBMITTER: Matsunaga K

PROVIDER: S-EPMC4686876 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Matsunaga Ken-ichiro K Kimoto Michiko M Hanson Charlotte C Sanford Michael M Young Howard A HA Hirao Ichiro I

Scientific reports 20151222

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 a ...[more]

PMID: 26690672

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