Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA
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 fibros...
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Book |
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Elsevier,
2017-06-01T00:00:00Z.
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| 001 | doaj_067d30ab42c94fd7a7632e3a5b0cfe2c | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Eva Schrom |e author |
| 700 | 1 | 0 | |a Maja Huber |e author |
| 700 | 1 | 0 | |a Manish Aneja |e author |
| 700 | 1 | 0 | |a Christian Dohmen |e author |
| 700 | 1 | 0 | |a Daniela Emrich |e author |
| 700 | 1 | 0 | |a Johannes Geiger |e author |
| 700 | 1 | 0 | |a Günther Hasenpusch |e author |
| 700 | 1 | 0 | |a Annika Herrmann-Janson |e author |
| 700 | 1 | 0 | |a Verena Kretzschmann |e author |
| 700 | 1 | 0 | |a Olga Mykhailyk |e author |
| 700 | 1 | 0 | |a Tamara Pasewald |e author |
| 700 | 1 | 0 | |a Prajakta Oak |e author |
| 700 | 1 | 0 | |a Anne Hilgendorff |e author |
| 700 | 1 | 0 | |a Dirk Wohlleber |e author |
| 700 | 1 | 0 | |a Heinz-Gerd Hoymann |e author |
| 700 | 1 | 0 | |a Dirk Schaudien |e author |
| 700 | 1 | 0 | |a Christian Plank |e author |
| 700 | 1 | 0 | |a Carsten Rudolph |e author |
| 700 | 1 | 0 | |a Rebekka Kubisch-Dohmen |e author |
| 245 | 0 | 0 | |a Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA |
| 260 | |b Elsevier, |c 2017-06-01T00:00:00Z. | ||
| 500 | |a 2162-2531 | ||
| 500 | |a 10.1016/j.omtn.2017.04.006 | ||
| 520 | |a 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. | ||
| 546 | |a EN | ||
| 690 | |a ACE2 | ||
| 690 | |a RNA therapy | ||
| 690 | |a cmRNA | ||
| 690 | |a modified mRNA | ||
| 690 | |a mRNA delivery | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Molecular Therapy: Nucleic Acids, Vol 7, Iss C, Pp 350-365 (2017) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S2162253117301567 | |
| 787 | 0 | |n https://doaj.org/toc/2162-2531 | |
| 856 | 4 | 1 | |u https://doaj.org/article/067d30ab42c94fd7a7632e3a5b0cfe2c |z Connect to this object online. |