Type 1 diabetes (T1D) is characterised by autoimmune destruction of pancreatic β-cells, yet current therapies primarily rely on systemic immunomodulation and do not directly preserve β-cell function. We have previously developed pancreas-targeted IL-22 biologics that suppress β-cell stress, reduce major histocompatibility complex class II (MHC II) expression, and promote immune tolerance. To improve manufacturability, reduce cost, and enable a scalable therapeutic platform, we have now translated this approach into targeted IL-22 mRNA therapeutics.
We engineered IL-22-targeted mRNA constructs that maintain pancreas-specific targeting and biological activity, recapitulating the tissue selectivity observed with our targeted biologics. In ongoing preclinical studies, both the targeted IL-22 biologic and the targeted IL-22 mRNA construct significantly delay diabetes onset in Non-Obese Diabetic (NOD) mice. Notably, targeted IL-22-mRNA demonstrates efficacy comparable to, or exceeding, anti-CD3 therapy, the current approved disease-modifying treatment for T1D, while providing a β-cell-directed mechanism that avoids broad systemic immunosuppression. These therapeutic effects are accompanied by preservation of β-cell function and maintenance of pancreas-specific targeting.
Together, these findings establish targeted IL-22-mRNA as a next-generation cytokine delivery platform that combines the precision of targeted biologics with the scalability and manufacturing advantages of mRNA technology, providing a promising disease-modifying strategy for T1D.