Author: Schrom, Eva; Huber, Maja; Aneja, Manish; Dohmen, Christian; Emrich, Daniela; Geiger, Johannes; Hasenpusch, Günther; Herrmann-Janson, Annika; Kretzschmann, Verena; Mykhailyk, Olga; Pasewald, Tamara; Oak, Prajakta; Hilgendorff, Anne; Wohlleber, Dirk; Hoymann, Heinz-Gerd; Schaudien, Dirk; Plank, Christian; Rudolph, Carsten; Kubisch-Dohmen, Rebekka
Title: Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA Document date: 2017_4_13
ID: tulmnb32_16
Snippet: Administration of recombinant human ACE2 in experimental liver 15 and lung fibrosis 21 showed the first promising results. However, longterm effects on collagen deposition in the lung were considered questionable 20 and increased the need for local ACE2 delivery with greater efficacy, two requirements that are feasible with the latest advances in RTT. In addition, limited understanding of the physiological relevance of soluble ACE2 and a limited .....
Document: Administration of recombinant human ACE2 in experimental liver 15 and lung fibrosis 21 showed the first promising results. However, longterm effects on collagen deposition in the lung were considered questionable 20 and increased the need for local ACE2 delivery with greater efficacy, two requirements that are feasible with the latest advances in RTT. In addition, limited understanding of the physiological relevance of soluble ACE2 and a limited terminal half-life of 10 hr for recombinant ACE2 protein in humans 33 urged us to verify that cmRNA-derived ACE2 protein is processed to a stably expressed transmembrane protein. After we verified full protein glycosylation in vitro and in vivo (Figures 2A and 4F) , a crucial step for protein trafficking and integration into the plasma membrane, we confirmed correct protein integration into the plasma membrane ( Figures 2B-2D) .
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