Nucleic Acid-to-Small Molecule Converter through Amplified Hairpin DNA Circuits |
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Authors: | Dr Kunihiko Morihiro Yasuhiro Tomida Daisuke Fukui Manami Hasegawa Prof Akimitsu Okamoto |
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Institution: | Department of Chemistry and Biotechnology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656 Japan |
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Abstract: | Many microRNAs (miRNAs) are characteristically found in cancer cells, making miRNAs promising marker biomolecules for cancer diagnosis and therapeutics. However, it is challenging to use miRNA as a cancer signature because it is difficult to convert the nucleic acid sequence information into molecular functionality. To address this challenge, we realize nucleic acid-to-small molecule converters using hairpin DNA circuits. Harnessing a Staudinger reduction as a trigger for the conversion, we constructed hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA) circuits that respond to oncogenic miR-21. Fluorophore and dye molecules were released in response to miR-21 through the HCR, providing fluorogenic and chromogenic readouts. Selective cytotoxicity in miR-21-abundant cells was realized by the CHA to release the anticancer drug SN-38. This would be the first example of selective activation of a small-molecule prodrug triggered by oncogenic miRNA in human living cells. |
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Keywords: | Antitumor Agents Dyes Nucleic Acids Prodrugs Self-Assembly |
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