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Geometry-Programmable Living Immunomaterials for Spatial Control of Innate Immune Signaling
Haoyuan Xu1, Xiangbowen Jin1, Xing Lu1
1Microbial Sensing and Imaging Analysis Laboratory, Institute of Functional Nano & Soft Materials & Collaborative Innovation Center of Suzhou Nano Science and Technology (NANO-CIC), Soochow University, Suzhou, Jiangsu, P. R. China.
Advanced Materials (Deerfield Beach, Fla.)
|July 20, 2026
Summary
Researchers engineered DNA origami to precisely control immune signaling geometry, enhancing STING activation. This living immunomaterial suppressed colorectal tumor growth by over 80% by activating innate immune responses.
Area of Science:
- Biotechnology
- Immunology
- Nanotechnology
Background:
- Immune ligand spatial organization critically influences cGAS-STING signaling pathways.
- Nanoscale geometry dictates the cooperative assembly and catalytic activity of cGAS.
- Understanding this spatial regulation is key to developing targeted immunotherapies.
Purpose of the Study:
- To engineer geometry-programmable DNA origami for precise control over double-stranded DNA (dsDNA) valency and spacing.
- To enhance cooperative cGAS clustering and STING activation through optimized nanoscale architecture.
- To develop a living immunomaterial for localized innate immune signaling in colorectal tumors.
Main Methods:
- Design and synthesis of geometry-programmable DNA origami structures.
- Systematic modulation of dsDNA ligand periodicity and valency.
- Integration of DNA origami with probiotic Escherichia coli Nissle 1917 for surface anchoring.
- In vivo testing in microsatellite-stable colorectal cancer models.
Main Results:
- Optimized DNA origami with 60-bp dsDNA ligands at ~16.3 nm periodicity showed twofold stronger STING signaling than free dsDNA.
- The biohybrid system demonstrated robust intratumoral STING activation and T-cell-inflamed immune remodeling.
- Significant suppression of colorectal tumor growth (~83.5%) was observed in vivo.
Conclusions:
- Geometry-programmable DNA origami can precisely control nanoscale architecture to drive innate immune signaling.
- A living immunomaterial interface can be created by integrating engineered DNA origami with bacteria.
- This biohybrid system shows therapeutic potential for localized cancer immunotherapy by harnessing the cGAS-STING pathway.
