Advanced science (Weinheim, Baden-Wurttemberg, Germany)Jul 6, 2026

mRNA Lipid Nanoparticle Vaccines Help Treat Autoimmune Disease in Animal Models

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 7, 2026

Abstract

Both systemic and intramuscular delivery of MOG_27-63 mRNA-loaded lipid nanoparticles reduced disease severity in experimental autoimmune encephalomyelitis.

mRNA lipid nanoparticles (LNPs) encoding disease-relevant autoantigens may help restore immune balance in autoimmune conditions.
Antigen-specific protection was also observed in a type 1 diabetes model.
The use of immunostimulatory LNPs challenges the belief that effective tolerance requires immune-silent LNPs.
Outcomes varied based on the identity of the antigens used, indicating their role in either promoting tolerance or immune activation.
Optimized LNPs were effective in targeting antigen-presenting cells in the liver and spleen, leading to specific immune responses.
Co-delivery of autoantigen mRNA with immunoregulatory molecules improved clinical outcomes in the experimental model.

Simplified

Autoimmune diseases like multiple sclerosis (MS) and type 1 diabetes (T1D) lack therapies that induce durable, antigen-specific immune tolerance. We investigated whether mRNA lipid nanoparticles (LNPs) encoding disease-relevant autoantigens could re-establish immune homeostasis in preclinical models. While mRNA-LNP microbial vaccines evoke strong effector immune responses, we show that both systemic and intramuscular delivery of MOG_27-63 mRNA-loaded LNPs attenuated disease severity in experimental autoimmune encephalomyelitis (EAE). Antigen-specific protection was similarly observed in a T1D adoptive transfer model. Therapeutic efficacy achieved using immunostimulatory LNPs challenges the current assumption that tolerogenic mRNA vaccines require immune-silent LNPs. Furthermore, divergent outcomes between autoantigens and irrelevant antigens suggest that antigen identity determines whether mRNA-LNPs promote immune tolerance or activation. Mechanistically, optimized LNPs efficiently targeted antigen-presenting cells (APCs) in the liver and spleen. This promoted a homeostatic APC phenotype and a hyporesponsive CD4⁺ T cell phenotype without inducing regulatory T cells (Tregs). Therefore, autoantigen mRNA was co-delivered with "immunoregulatory" mRNAs encoding cytokines (IL-2 mutein) or chemokines (CCL1) known to enhance Treg expansion and recruitment. This co-delivery further improved clinical outcomes in EAE. Together, these findings demonstrate that systemic and intramuscular treatment with mRNA-LNPs encoding autoantigens alongside immunoregulatory molecules represents a promising strategy for antigen-specific immunotherapy in autoimmune diseases.

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Funding

Competing interests

The research is funded by etherna Immunotherapies NV. Karen Beets, Carlo Heirman, Jurgen Van den Heuvel, Bart Vanderborght, Ismael Varela, Roxanne Nouille, Lotte Jacobs, Jessica Filtjens, Sabah Kasmi, Elise Seynaeve, Veronica Mavrovouna, Jana De Vrieze, Florence Lambolez, and Stefaan De Koker are employees of etherna Immunotherapies NV and may hold stock in the company.

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mRNA Lipid Nanoparticle Vaccines Help Treat Autoimmune Disease in Animal Models

Abstract

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Funding

Competing interests

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