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Kinetically Programmed Signaling Cascades for Molecular Detection.

Guichi Zhu1, Dominic Lauzon2, Carl Prévost-Tremblay3

  • 1Institut de Génie Biomédical, Département de Pharmacologie et Physiologie, Université de Montréal, Montréal, Quebec H3T 1J4, Canada.

Journal of the American Chemical Society
|October 16, 2025
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Summary
This summary is machine-generated.

This study introduces a DNA-based signaling cascade where programming reaction kinetics enhances signal output. This bioinspired system enables rapid detection of molecules and can be adapted for at-home therapeutic drug monitoring.

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Area of Science:

  • Synthetic biology
  • Chemical kinetics
  • Molecular engineering

Background:

  • Cellular signaling cascades efficiently process stimuli for homeostasis.
  • Bioinspired chemical systems are emerging for applications in synthetic biology, computing, drug delivery, and biosensing.
  • Programming thermodynamics is explored, but kinetic programming's impact on bioinspired cascades is understudied.

Purpose of the Study:

  • To investigate the effect of kinetic programming on the performance of a DNA-based signaling cascade.
  • To develop a modular DNA cascade for measuring specific molecule concentrations.
  • To demonstrate the cascade's adaptability for detecting diverse analytes and enabling point-of-care diagnostics.

Main Methods:

  • Leveraged DNA chemistry's modularity and programmability.
  • Designed a four-module (input, receptor, processor, output) signaling cascade.
  • Characterized intrinsic rate constants of molecular interactions and performed simulations and experiments.

Main Results:

  • Demonstrated that kinetic programming significantly enhances the rate, gain, and sensitivity of the signaling cascade.
  • Successfully adapted the cascade for detecting four different molecules (small molecules and proteins).
  • Showcased the cascade's potential for a rapid, one-step electrochemical sensor for therapeutic drug monitoring (TDM).

Conclusions:

  • Kinetic programming is a powerful strategy to optimize signaling cascade performance.
  • The developed DNA-based cascade is versatile, modular, and adaptable for various sensing applications.
  • This approach could streamline complex chemical workflows into rapid, single-step reactions for diverse applications.