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Related Experiment Video

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Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo

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Published on: September 18, 2014

Intracellular DNA network assembly triggered by microRNA and telomerase for imaging-guided STING hyperactivation.

Yaru Cheng¹, Youming Feng², Lei Shuai³

¹Marshall Laboratory of Biomedical Engineering, Precision Medicine and Health Research Institute, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, China; Beijing Center for Disease Prevention and Control, Beijing, 100013, China.

Biosensors & Bioelectronics

|February 22, 2026

Summary

This study presents a novel nanoplatform for cancer immunotherapy that precisely activates STING in tumor cells using microRNA and telomerase. This imaging-guided approach enhances STING activation, leading to potent antitumor immunity with reduced toxicity.

Keywords:

Spatiotemporal DNA assembly Telomerase activity Tumor imaging cGAS-STING miRNA-155

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Area of Science:

Biotechnology
Immunology
Nanomedicine

Background:

Clinical translation of cGAS-STING activation for cancer immunotherapy is hindered by nonspecific activation and off-target toxicities.
Targeted activation of the cGAS-STING pathway is crucial for effective and safe cancer immunotherapy.

Purpose of the Study:

To design a strategy for intracellular DNA network assembly triggered by microRNA (miRNA) and telomerase for imaging-guided STING hyperactivation.
To develop a nanoplatform (DiG-DNA) that specifically activates in tumor cells overexpressing miRNA-155 and telomerase.

Main Methods:

Utilized miRNA-responsive hairpin DNAs and telomerase-activatable linear DNA to form a nanoplatform (DiG-DNA).
Engineered cascade activation involving miRNA-155 initiated catalytic hairpin assembly (CHA) and telomerase-driven strand elongation.
Monitored DNA network assembly in real time using multiplexed fluorescence recovery (Cy3/Cy5) for imaging guidance.

Main Results:

DiG-DNA remained silent in normal cells but assembled into a dense 3D DNA network (N-DNA) within tumor cells.
In situ-formed N-DNA potently activated cGAS, promoted liquid-liquid phase separation (LLPS), and robustly activated STING.
Demonstrated strong tumor inhibition in vivo, confirming high spatial specificity and effective antitumor immunity.

Conclusions:

Developed an intracellular DNA network assembly strategy for precise and imaging-guided cancer immunotherapy.
This approach ensures specificity through endogenous biomarker triggers, offering a new paradigm for STING-based therapies.
The nanoplatform enables controlled STING hyperactivation, leading to significant antitumor effects with potential for reduced toxicity.