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Characterization of a transmembrane-activating STING agonist using genetically humanized mice
Nobuyo Mizuno1, Jinu Abraham1, Kevin Jimenez-Perez1
1Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, USA.
Cell Reports
|June 2, 2026
Summary
Researchers developed humanized STING mice to study human-selective STING agonists. These agonists, targeting the STING transmembrane region, show potential as vaccine adjuvants and cancer therapies.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Stimulator of interferon genes (STING) is a key pattern recognition receptor.
- STING activation triggers type I interferon and inflammatory responses.
- Clinical trials of STING agonists have faced challenges, necessitating new research models.
Purpose of the Study:
- To develop and characterize human-selective STING agonists.
- To establish a genetically humanized STING mouse model for in vivo testing.
- To investigate the molecular and immune effects of transmembrane STING agonism.
Main Methods:
- Synthesis of human-selective STING agonists.
- Generation of genetically humanized STING mice.
- In vivo immune characterization of agonist effects.
Main Results:
- The lead molecule binds to the STING transmembrane region.
- Transmembrane STING agonism exhibits distinct molecular and immune profiles compared to conventional agonists.
- Humanized mice enabled in vivo evaluation of human-selective agonists.
Conclusions:
- Genetically humanized STING mice are effective for studying human-selective STING agonists.
- Transmembrane STING agonists offer a promising avenue for vaccine adjuvants and cancer therapeutics.
- This study provides a comprehensive in vivo immune characterization of transmembrane STING agonism.
