Abstract

DNA aptamers have potential for disease diagnosis and as therapeutics, particularly when interfaced with programmable molecular technology. Here we have combined DNA aptamers specific for the malaria biomarker Plasmodium falciparum lactate dehydrogenase (PfLDH) with a DNA origami scaffold. Twelve aptamers that recognise PfLDH were integrated into a rectangular DNA origami and atomic force microscopy demonstrated that the incorporated aptamers preserve their ability to specifically bind target protein. Captured PfLDH retained enzymatic activity and protein-aptamer binding was observed dynamically using high-speed AFM. This work demonstrates the ability of DNA aptamers to recognise a malaria biomarker whilst being integrated within a supramolecular DNA scaffold, opening new possibilities for malaria diagnostic approaches based on DNA nanotechnology.

Highlights

  • Effect ascribed to the distortion of the aptamer tail[10]

  • We based our DNA origami template on a standard rectangle design[25] and employed aptamer sequences known to bind to PfLDH, whose structure and interaction with target protein are known in unprecedented detail[10]

  • In order to incorporate these aptamers into DNA origami, a staple sequence complementary to part of the M13 DNA origami template strand was added at the 5′ end of the aptamer

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Summary

ATACGTAAAAGTACAA TCCTCTTTTGAGGAACAAGTTTTCTTGT CGGAGATTTCATCAAG

The production of a rectangular DNA origami scaffold integrated with the PfLDH-binding DNA aptamer[10]. We demonstrate that upon integration with DNA origami, the aptamers are able to retain the ability to bind to PfLDH. This is the first attempt to use PfLDH in conjunction with DNA origami as an initial step towards the goal of more complex “smart” malaria detection/treatment devices

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