| Autor: |
Eva Schrom, Maja Huber, Manish Aneja, Christian Dohmen, Daniela Emrich, Johannes Geiger, Günther Hasenpusch, Annika Herrmann-Janson, Verena Kretzschmann, Olga Mykhailyk, Tamara Pasewald, Prajakta Oak, Anne Hilgendorff, Dirk Wohlleber, Heinz-Gerd Hoymann, Dirk Schaudien, Christian Plank, Carsten Rudolph, Rebekka Kubisch-Dohmen |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 7, Iss C, Pp 350-365 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1016/j.omtn.2017.04.006 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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