Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Krienke, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kolb, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Diken, Elif UNSPECIFIED UNSPECIFIED UNSPECIFIED Streuber, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirchhoff, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Bukur, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Akilli-Ozturk, Ozlem UNSPECIFIED UNSPECIFIED UNSPECIFIED Kranz, Lena M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Berger, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Petschenka, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED Diken, Mustafa UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreiter, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Yogev, Nir UNSPECIFIED UNSPECIFIED UNSPECIFIED Waisman, Ari UNSPECIFIED UNSPECIFIED UNSPECIFIED Kariko, Katalin UNSPECIFIED UNSPECIFIED UNSPECIFIED Tureci, Ozlem UNSPECIFIED UNSPECIFIED UNSPECIFIED Sahin, Ugur UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language T-CELLS; CNS; SUPPRESSION; EXPRESSION; THERAPY Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59083