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. 2015 Jun 30;23(9):1456–1464. doi: 10.1038/mt.2015.103

Figure 2.

Figure 2

Sequence engineering of mRNA enables high level protein expression in vivo. (a) Engineered, unmodified mouse Epo mRNA yields higher protein levels in mice than the corresponding pseudouridine modified sequence. 1 μg of either unmodified or pseudouridine modified mRNA encoding erythropoietin was complexed with TransIT and intraperitoneally injected into mice. Serum erythropoietin (EPO) levels were determined at different times (1, 2, or 3 days) after administration. (b) Low nanogram doses of engineered, unmodified mouse Epo mRNA give rise to substantial protein levels in murine serum. The indicated amounts of TransIT-complexed unmodified Epo mRNA were administered intraperitoneally. As a control, 100 U of recombinant human EPO protein (hEPO) were given i.p. Serum EPO levels were determined 24 hours after treatment. unmod, engineered mRNA harboring the nucleotides A, U, G, and C; ψ, engineered mRNA in which pseudouridine replaces U. n = 4 for all groups.