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. 2018 Sep 24;28(5):285–296. doi: 10.1089/nat.2018.0734

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© Ruchi Jain et al. 2018; Published by Mary Ann Liebert, Inc.

This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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FIG. 4. — miRNAs can suppress off-target expression in mammals. (a) Schematic representation of mRNA with a miRts in the 3′ UTR. (b–d) miRts incorporation in mRNA enables protein suppression in rodents upon mRNA delivery. Serum Epo levels 6 h after MC3-encapsulated or L2000-complexed 1-methyl-pseudouridine (m¹Ψ) mRNA encoding Epo was administered intravenously to (b) mice or (c) rats. (d) Total flux (photons/s) and serum Epo levels 6 h after MC3-encapsulated m¹Ψ mRNAs encoding Luc and Epo were administered intravenously to “chimeric” mice (mouse hepatocytes replaced with human hepatocytes). (e) miRts incorporation in mRNA enables protein suppression in nonhuman primates upon mRNA delivery. Serum Epo levels 6 h after MC3-encapsulated m¹Ψ mRNA encoding Epo was administered intravenously to African green monkey. (f) Schematic representation of an mRNA with two different miRts's in the 3′ UTR. (g) Incorporation of different miRts's in mRNA enables protein suppression in multiple tissues upon mRNA delivery. Total flux (photons/s) from liver and spleen 6 h after MC3-encapsulated m¹Ψ mRNA encoding Luc was intravenously administered to mice. Error bars represent standard deviation in the figure. Luminescence/Epo expression generated upon intravenous administration of miRts-containing mRNA was compared with levels with CTRL mRNA, and P values were generated by Prism using the unpaired, two-tailed t-test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.