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Rational Design Strategies for Stimuli-Responsive DNAzymes Using Modified and Artificial Nucleotides
Yusuke Takezawa1, Mitsuhiko Shionoya2
1Chemistry and Materials Program, College of Engineering, Shibaura Institute of Technology, Saitama, Japan.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|January 21, 2026
Summary
This review explores rational design strategies for stimuli-responsive DNAzymes, focusing on modified nucleotides for controllable activation in molecular sensing and DNA nanotechnology.
Area of Science:
- Molecular Biology
- Biotechnology
- Nanotechnology
Background:
- DNA is a versatile building block in molecular technology.
- DNAzymes, catalytic DNA, show potential in diagnostics, therapeutics, and DNA nanotechnology.
- Stimuli-responsive DNAzymes are crucial for advanced applications but require general design strategies.
Purpose of the Study:
- To review rational design strategies for stimuli-responsive RNA-cleaving DNAzymes.
- To focus on using modified and artificial nucleotides for controllable activation.
- To provide a toolkit for molecular sensing and DNA nanotechnology.
Main Methods:
- Sequence engineering and chemical modification of existing DNAzymes.
- Utilizing modified and artificial nucleotides.
- Discussing strategies like split DNAzyme reconstitution, strand cleavage/ligation, removable blocking oligonucleotides, labile protecting groups, and conformational switching.
Main Results:
- Several rational design strategies for stimuli-responsive DNAzymes are presented.
- These strategies enable externally controllable activation mechanisms.
- The intrinsic catalytic activity of DNAzymes is maintained.
Conclusions:
- Rational design of stimuli-responsive DNAzymes using modified nucleotides offers a valuable toolkit.
- These engineered DNAzymes are suitable for advanced molecular sensing and DNA nanotechnology applications.
- Controllable activation is key for expanding DNAzyme utility.
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