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Schrom, E.* ; Huber, M.* ; Aneja, M.K.* ; Dohmen, C.* ; Emrich, D.* ; Geiger, J.* ; Hasenpusch, G.* ; Herrmann-Janson, A.* ; Kretzschmann, V.* ; Mykhailyk, O.* ; Pasewald, T.* ; Oak, P. ; Hilgendorff, A. ; Wohlleber, D.* ; Hoymann, H.* ; Schaudien, D.* ; Plank, C.* ; Rudolph, C.* ; Kubisch-Dohmen, R.*

Translation of angiotensin-converting enzyme 2 upon liver- and lung-targeted delivery of optimized chemically modified mRNA.

Mol. Ther. Nucleic Acids 7, 350-365 (2017)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis. Promising results have been reported for recombinant angiotensin-converting enzyme 2 ( ACE2) protein administration in experimental liver and lung fibrosis. However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form. For this purpose, we advanced the latest RNA technology for liver-and lung-targeted ACE2 translation. We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA) leads to robust translation of fully matured, membrane-anchored ACE2 protein. In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application. Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver-and lung-targeted translation of significant amounts of ACE2 protein, respectively. In summary, we provide evidence that RNA transcript therapy (RTT) is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Ace2 ; Rna Therapy ; Cmrna ; Mrna Delivery ; Modified Mrna; Idiopathic Pulmonary-fibrosis; Alveolar Epithelial-cells; Hepatic Stellate Cells; Induced Apoptosis; Receptor; Expression; Therapeutics; Ace2; Mice; Angiotensin-converting-enzyme-2
ISSN (print) / ISBN 2162-2531
e-ISSN 2162-2531
Zeitschrift Molecular therapy - Nucleic Acids
Quellenangaben Band: 7, Heft: , Seiten: 350-365 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus