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An Autocatalytic Molecular Sensor Enables Rapid, Sensitive, and One-Pot Detection of Nucleic Acids
Xue Li1, Zhihao Xu1, Xiaowei Ma1
1Institute of Molecular Medicine, Department of Laboratory Medicine, Department of Urology, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
ACS Nano
|June 15, 2026
Summary
We developed RAPID, a novel biomimetic assay for rapid and sensitive nucleic acid detection. This assay enables quick, cost-effective disease diagnosis using minimal equipment, advancing liquid biopsy applications.
Area of Science:
- Biomolecular Engineering
- Molecular Diagnostics
- Virology
Background:
- Circulating nucleic acids show promise as disease biomarkers.
- Current detection methods lack speed, sensitivity, and cost-effectiveness.
- Clinical application of nucleic acid biomarkers is limited by assay technology.
Purpose of the Study:
- To develop a rapid, sensitive, and instrument-minimal nucleic acid detection assay.
- To create a biomimetic assay inspired by viral replication mechanisms.
- To enable efficient molecular diagnostics for clinical applications like liquid biopsy.
Main Methods:
- Developed RAPID, a one-step, one-pot isothermal assay.
- Utilized duck circovirus (DCV) endonuclease for autocatalytic amplification.
- Integrated rolling circle amplification (RCA) with DCV cleavage for exponential signal generation.
- Enabled smartphone-based fluorescence detection.
Main Results:
- Achieved rapid (∼10 min) and ultrasensitive (attomolar) nucleic acid detection.
- Demonstrated RNA extraction-free detection of microRNAs and viral RNAs.
- Successfully discriminated prostate cancer from benign prostatic hyperplasia using miRNA profiling.
- Accurately detected influenza A virus in point-of-care settings.
Conclusions:
- RAPID assay offers a simple, rapid, and sensitive method for nucleic acid detection.
- The assay has significant clinical translational potential for liquid biopsy and point-of-care diagnostics.
- Biomimetic approaches can overcome limitations in current molecular diagnostic technologies.
