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Published on: December 8, 2023
Defect Engineering of DNA Origami ROS Sensors for Portable Urinalysis
Shuangye Zhang1,2, Zhe Liu1, Yuanhao Wang3
1State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center For Transformative Molecules, Zhang Jiang Institute For Advanced Study and National Center For Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
Researchers developed DNA origami ROS sensors (DOSs) for early, noninvasive detection of oxidative stress. These sensors enable portable urinalysis, identifying acute liver injury hours before traditional tests.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Molecular Diagnostics
Background:
- Translating in situ dynamic signaling molecule changes into clinical readouts is challenging for noninvasive diagnostics.
- Reactive oxygen species (ROS) are key signaling mediators implicated in various diseases.
- Current diagnostic methods for oxidative stress-related conditions often lack sensitivity and timeliness.
Purpose of the Study:
- To develop defect-programmed DNA origami ROS sensors (DOSs) for portable urinalysis.
- To establish a correlation between defect number and ROS-triggered degradation kinetics.
- To create a generalizable platform for early, noninvasive diagnosis of ROS-related diseases.
Main Methods:
- Designed triangular DNA origami (DO) nanostructures with programmable discontinuity defects.
- Engineered DOSs by assembling targeting and signaling modules onto DO.
- Validated DOSs in a murine model of acute liver injury (ALI) for ROS detection via urinary signals.
Main Results:
- A positive correlation was established between defect number and ROS-triggered degradation kinetics.
- DOSs selectively accumulated in the liver, fragmented upon ROS exposure, and produced quantifiable urinary signals.
- DOSs detected ALI onset 4 hours earlier than ALT testing, with an AUC of 0.94.
Conclusions:
- Defect-programmed DNA origami sensors offer a novel approach for portable urinalysis of localized oxidative stress.
- This defect-engineering strategy provides a generalizable platform for early, noninvasive diagnosis of ROS-related diseases.
- DOSs demonstrate significant potential for advancing diagnostics in conditions associated with oxidative stress.
