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Updated: Jun 12, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
A DNA Molecular Logic Circuit for Precise Tumor Identification
Yingyu Sima1, Lili Ai1, Linlin Wang1
1Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
Abstract:
Tumor-associated antigens (TAAs) are not exclusively expressed in cancer cells, inevitably causing the "on target, off tumor" effect of molecular recognition tools. To achieve precise recognition of cancer cells, by using protein tyrosine kinase 7 (PTK7) as a model TAA, a DNA molecular logic circuit Aisgc8 was rationally developed by arranging H+-binding i-motif, ATP-binding aptamer, and PTK7-targeting aptamer Sgc8c in a DNA sequence. Aisgc8 output the conformation of Sgc8c to recognize PTK7 on cells in a simulated tumor microenvironment characterized by weak acidity and abundant ATP, but not in a simulated physiological environment. Through in vitro and in vivo results, Aisgc8 demonstrated its ability to precisely recognize cancer cells and, as a result, displayed excellent performance in tumor imaging. Thus, our studies produced a simple and efficient strategy to construct DNA logic circuits, opening new possibilities to develop convenient and intelligent precision diagnostics by using DNA logic circuits.
Insights
Researchers developed a DNA logic circuit to precisely target cancer cells expressing protein tyrosine kinase 7 (PTK7). This innovation enables accurate tumor imaging and diagnostics by distinguishing cancer cells in specific microenvironments.
Area of Science:
- Biotechnology
- Molecular Biology
- Cancer Research
Background:
- Tumor-associated antigens (TAAs) are often expressed on both cancer and normal cells, leading to the "on target, off tumor" effect in diagnostic and therapeutic tools.
- Developing molecular recognition tools that can precisely identify cancer cells while sparing healthy tissues remains a significant challenge in oncology.
Purpose of the Study:
- To design and validate a DNA molecular logic circuit for the specific recognition of cancer cells.
- To utilize protein tyrosine kinase 7 (PTK7) as a model TAA for demonstrating the circuit's precision.
- To establish a strategy for developing intelligent DNA-based diagnostic tools.
Main Methods:
- A DNA molecular logic circuit, termed Aisgc8, was rationally designed by integrating an H+-binding i-motif, an ATP-binding aptamer, and the PTK7-targeting aptamer Sgc8c.
- The circuit's functionality was evaluated in simulated tumor microenvironments (weak acidity, abundant ATP) versus simulated physiological environments.
- In vitro and in vivo experiments were conducted to assess the circuit's cancer cell recognition accuracy and tumor imaging performance.
Main Results:
- The Aisgc8 DNA logic circuit successfully output the Sgc8c aptamer's conformation to recognize PTK7-expressing cells specifically in the simulated tumor microenvironment.
- The circuit demonstrated high specificity, distinguishing cancer cells from normal cells by not activating in the simulated physiological environment.
- Aisgc8 exhibited excellent performance in tumor imaging, confirming its capability for precise cancer cell recognition.
Conclusions:
- A simple and efficient strategy for constructing DNA logic circuits was developed.
- The Aisgc8 circuit provides a precise method for recognizing cancer cells based on their specific microenvironment.
- This approach opens new avenues for developing convenient and intelligent precision diagnostics using DNA logic circuits.
