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Peptide-Programmable DNAzyme Converter for Artificial Autocatalytic Gene Regulation.

Qingqing Zhang1, Jian Hao2,3,4, Yuqiu He1

  • 1College of Chemistry and Molecular Sciences, Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430072, P. R. China.

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|September 10, 2025
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Summary
This summary is machine-generated.

We developed iPAD, a novel peptide-programmed deoxyribonuclease system for protease sensing. This platform enables efficient gene silencing and autocatalytic gene regulation for enhanced biosensing and theranostics.

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Chemical Biology

Background:

  • Effective protein-to-gene transduction is crucial for cellular information processing but faces challenges.
  • Existing strategies are often complex and inefficient.

Purpose of the Study:

  • To develop a simple, protease-guided autocatalytic gene silencing platform for versatile DNA readout signals.
  • To create a universal protease sensing platform for biosensing and bioengineering.

Main Methods:

  • Designed a protease-responsive cationic peptide (PP) to modulate DNAzyme (Dz) activity.
  • Utilized molecular dynamic simulations to validate peptide-oligomerization-mediated Dz regulation.
  • Applied the platform to detect Caspase-3 and thrombin for tumor therapeutic evaluation.

Main Results:

  • The iPAD system converts protease recognition into DNA readout signals.
  • Achieved robust and accurate protease activity monitoring via protease-specific cleavage of PP.
  • Demonstrated successful application in early evaluation of tumor therapeutic efficacy.
  • Constructed an autocatalytic gene regulation platform for accelerated tumor cell apoptosis.

Conclusions:

  • The iPAD system offers a simple yet intelligent toolbox for high-performance biosensing and bioengineering.
  • Paves the way for new strategies in smart theranostic research.
  • Enables self-adaptive upregulation of apoptotic proteases for enhanced tumor cell apoptosis.