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Independent control of the thermodynamic and kinetic properties of aptamer switches

Author

Listed:
  • Brandon D. Wilson

    (Stanford University)

  • Amani A. Hariri

    (Stanford University)

  • Ian A. P. Thompson

    (Stanford University)

  • Michael Eisenstein

    (Stanford University
    Stanford University)

  • H. Tom Soh

    (Stanford University
    Stanford University
    Chan Zuckerberg Biohub)

Abstract

Molecular switches that change their conformation upon target binding offer powerful capabilities for biotechnology and synthetic biology. Aptamers are useful as molecular switches because they offer excellent binding properties, undergo reversible folding, and can be engineered into many nanostructures. Unfortunately, the thermodynamic and kinetic properties of the aptamer switches developed to date are intrinsically coupled, such that high temporal resolution can only be achieved at the cost of lower sensitivity or high background. Here, we describe a design strategy that decouples and enables independent control over the thermodynamics and kinetics of aptamer switches. Starting from a single aptamer, we create an array of aptamer switches with effective dissociation constants ranging from 10 μM to 40 mM and binding kinetics ranging from 170 ms to 3 s. Our strategy is broadly applicable to other aptamers, enabling the development of switches suitable for a diverse range of biotechnology applications.

Suggested Citation

  • Brandon D. Wilson & Amani A. Hariri & Ian A. P. Thompson & Michael Eisenstein & H. Tom Soh, 2019. "Independent control of the thermodynamic and kinetic properties of aptamer switches," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13137-x
    DOI: 10.1038/s41467-019-13137-x
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    Cited by:

    1. Alex M. Yoshikawa & Alexandra E. Rangel & Liwei Zheng & Leighton Wan & Linus A. Hein & Amani A. Hariri & Michael Eisenstein & H. Tom Soh, 2023. "A massively parallel screening platform for converting aptamers into molecular switches," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Nicolò Maganzini & Ian Thompson & Brandon Wilson & Hyongsok Tom Soh, 2022. "Pre-equilibrium biosensors as an approach towards rapid and continuous molecular measurements," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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