Researchers led by Dr. Ling Li from the Department of Occupational and Environmental Health, West China School of Public Health/West China Hospital of Sichuan University, have revealed that DNA origami technology is a promising strategy for spatial regulation of cell signaling, providing a typical example for developing targeted drugs for diseases by spatially regulating cell signaling pathways. Their findings were published in the journal "Nature Materials."
Rheumatoid arthritis (RA) is a common autoimmune disease characterized by synovial inflammation and joint destruction, significantly impacting patients' quality of life. The pathogenesis of RA involves abnormal activation of various immune cells and release of inflammatory mediators. Despite advances in modern medicine, the treatment of RA remains challenging. The CD95/CD95 ligand (CD95L) signaling pathway plays a crucial role in regulating immune cell apoptosis and immune tolerance.
The study developed a reconfigurable two-dimensional DNA origami structure to precisely arrange CD95L into a two-dimensional hexagonal geometric pattern, accurately regulating the activation of the CD95/CD95L immune signaling pathway. This origami structure can reversibly switch between closed and open states in response to pH changes, achieving specific control of immune cell signal transduction in inflamed joints.
Using this technology, the research team successfully modulated immune cell signaling. In a collagen-induced arthritis mouse model, locally ablating immune cells in inflamed synovial tissue significantly alleviated chronic inflammation, promoted local immune tolerance, improved joint damage, and effectively mitigated the pathological process of RA. The study demonstrates that DNA origami technology is a promising strategy for spatial regulation of cell signaling, providing a typical example for developing targeted drugs for diseases by spatially regulating cell signaling pathways.
For more information, refer to the original paper at: https://doi.org/10.1038/s41563-024-01865-5
