Systemic modulation of immune tolerance to treat periodontitis via mir-122 inhibition
This research explores the modulation of immune tolerance to treat periodontitis by inhibiting miR-122. Utilizing small molecules to reduce miR-122 expression, the study aims to validate effective treatments in animal models, targeting immune response and bone loss attenuation.
Overview
This research initiative focuses on overcoming periodontitis through the modulation of immune tolerance by targeting miR-122. The proposed approach involves the use of small molecules to inhibit the expression and secretion of miR-122, a crucial factor in the regulation of immune responses. Preliminary results indicate that miR-122 knockout (KO) mice show significant resistance to infections, suggesting that miR-122 plays a pivotal role in immune regulation and the progression of periodontitis. The ultimate goal is to identify effective small molecules that can halt or reverse periodontitis progression in animal models, paving the way for potential therapeutic applications in humans.
Technical specifications
- Small Molecule Development: The project involves the development of small compounds that inhibit RORa, a transcription factor essential for miR-122 expression.
- Model Testing: The compounds will be tested in ligature-induced periodontitis models and further validated using an oral gavage model with P. gingivalis.
- Comprehensive Analysis: Readouts will include immune response assessments, microCT imaging, and histological analysis to evaluate the efficacy of the treatment.
- Future Aims: The research includes generating new RORa reverse agonists, testing their effects on miR-122 in vitro, and assessing their efficacy in various in vivo models with different delivery systems.
Technology readiness level
Currently, the technology is at TRL 3, indicating experimental proof of concept. The research involves in vitro and in vivo testing to further validate the efficacy of the identified small molecules in controlling periodontitis.
About Hadassah Medical Center
Hadassah Medical Center is a large academic medical organization in Jerusalem, operating two university hospitals with a translational, patient-centered character. Research laboratories are integrated with clinical departments, enabling movement between laboratory studies, patient care, and clinical investigation within one environment. Industry-facing infrastructure includes core laboratory services, GMP-grade space, tissue banking, advanced imaging and animal facilities, and sponsored clinical-trial capacity. Collaboration with the Hebrew University broadens access to academic expertise and shared facilities, while Hadasit supports intellectual property, licensing, and commercialization. Research is backed by the U.S. National Institutes of Health, the European Union, the Israel Science Foundation, philanthropic sources, and companies.
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