Krienke, Christina, Kolb, Laura, Diken, Elif, Streuber, Michael, Kirchhoff, Sarah, Bukur, Thomas, Akilli-Ozturk, Ozlem, Kranz, Lena M., Berger, Hendrik, Petschenka, Jutta, Diken, Mustafa, Kreiter, Sebastian, Yogev, Nir, Waisman, Ari, Kariko, Katalin, Tureci, Ozlem and Sahin, Ugur (2021). A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science, 371 (6525). S. 146 - 155. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1095-9203

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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 (m1 Psi 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 m1 Psi mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (T-reg cell) populations. Notably, these T-reg cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Krienke, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolb, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diken, ElifUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Streuber, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirchhoff, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bukur, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Akilli-Ozturk, OzlemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kranz, Lena M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berger, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petschenka, JuttaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diken, MustafaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreiter, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yogev, NirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waisman, AriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kariko, KatalinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tureci, OzlemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sahin, UgurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-590837
DOI: 10.1126/science.aay3638
Journal or Publication Title: Science
Volume: 371
Number: 6525
Page Range: S. 146 - 155
Date: 2021
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1095-9203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
T-CELLS; CNS; SUPPRESSION; EXPRESSION; THERAPYMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59083

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