Th2 Suppression Through Antigen Liver Expression Using mRNA-LNP Technology

Background: Messenger RNA-lipid nanoparticle (mRNA-LNP) is a cutting-edge nucleic acid intracellular delivery technology. Although the clinical use of the mRNA vaccine is being actively developed, the use of mRNA-LNP technology in common diseases such as allergies is still being investigated. The purpose of this study is to test if immune response can be suppressed when an antigen is expressed in mice liver tissue with mRNA-LNP technology. Methods: We first designed mRNA which the ovalbumin (OVA) antigen expresses on the surface of the cells, and synthesized mRNA were encapsulated into LNP. This OVA-mRNA-LNP was evaluated with an OVA-sensitized mouse model. Splenocytes from OVA-sensitized mice were cultured with ex vivo OVA stimulation for Th2 cytokine production and Treg population analysis. Furthermore, OVA-mRNA-LNP was evaluated by both prophylactic and therapeutic administration in an OVA-induced mice airway inflammation model. Results: Th2 cytokines such as IL-4 and IL-5 were suppressed and the Treg population was increased in ex vivo OVA-stimulated splenocytes isolated from the OVA-mRNA-LNP administered group. Moreover, suppression of Th2 cytokines in Bronchoalveolar Lavage Fluid (BALF) from both the prophylactic and therapeutic OVA-mRNA-LNP administered cohort was observed (40-80% reduction in Th2 cytokines). Conclusions: The data suggests that mRNA-LNP technology, which is a safe, non-viral gene delivery system, can be an effective approach to suppress allergen-induced inflammation by expressing antigen in the liver tissue.