Title: A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis

Author: Christina Krienke, Laura Kolb, Elif Diken, Michael Streuber, Sarah Kirchhoff, Thomas Bukur, zlem Akilli-ztürk, Lena M. Kranz, Hendrik Berger, Jutta Petschenka, Mustafa Diken, Sebastian Kreiter, Nir Yogev, Ari Waisman, Katalin Karikó, zlem Türeci, Ugur Sahin

Issue&Volume: 2021/01/08

Abstract: The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1Ψ mRNA) coding for disease-related autoantigens results in antigen presentation on splenic CD11c+ antigen-presenting cells in the absence of costimulatory signals. In several mouse models of multiple sclerosis, the disease is suppressed by treatment with such m1Ψ mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (Treg cell) populations. Notably, these Treg cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens.

DOI: 10.1126/science.aay3638

Source: https://science.sciencemag.org/content/371/6525/145