Therapeutic vaccination with auto-antigen mRNA loaded tolerizing lipid nanoparticles cures murine model of multiple sclerosis

Abstract

Introduction: Current treatments for autoimmunity are based on general immune suppression, while a true cure is still lacking. Therefore, efforts are being made to re-establish long-term tolerance in an antigen-specific manner. Objectives/Aims: We aim to develop a validated mRNA based tolerizing customized lipid nanoparticle (Tol-cLNP) vaccine to induce antigen-specific tolerance in MS and other autoimmune diseases. To achieve this, the antigen needs to be presented in an immune-silent manner. Methods: Tol-cLNP were loaded with myelin oligodendrocyte glycoprotein (MOG) mRNA and used for vaccination in different in vivo models. Results: Our data show that our MOG mRNA Tol-cLNP vaccine is indeed immune-silent, as shown by reduced interferon regulatory pathway activation in comparison to standard methods. Next,