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_7
Snippet: After having successfully verified that the sequence of ACE2 cmRNA leads to the translation of an active membrane-bound form of ACE2 www.moleculartherapy.org protein, we wanted to further optimize the sequence for strong protein translation. Therefore, we designed eight different ACE2 cmRNA sequences, sharing the same open reading frame (ORF) encoding ACE2, a C1-m7G cap, and a poly(A) tail of $120 nucleotides, which was found to be the optimal le.....
Document: After having successfully verified that the sequence of ACE2 cmRNA leads to the translation of an active membrane-bound form of ACE2 www.moleculartherapy.org protein, we wanted to further optimize the sequence for strong protein translation. Therefore, we designed eight different ACE2 cmRNA sequences, sharing the same open reading frame (ORF) encoding ACE2, a C1-m7G cap, and a poly(A) tail of $120 nucleotides, which was found to be the optimal length. 40 In addition to the natural ACE2 mRNA sequence, we introduced three different modifications of the UTRs known for a high level of protein translation [41] [42] [43] : namely, a minimal 5 0 UTR, a human alpha globin (haG) 5 0 UTR, and a cytochrome b-245 alpha poly-peptide (CYBA) 5 0 with 3 0 UTR. For all four sequences, we designed one natural version and one codon-optimized version of the ORF.
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