Figure 4
From: Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
Expression of human AAT protein following intravenous injection of modified mRNA in wild type mouse. Modified mRNA in LNP formulation was administered as a one-time intravenous (tail-vein) injection at 0.5 mg/kg into C57BL/6 mice (n = 3) and liver tissue was collected 1 hour; 24 hours and 48 hours post injection. (a) Liver tissue was stained for human AAT protein, which revealed a robust intracellular expression in hepatocytes followed by accumulation in the sinusoidal space, scalebar 100 µm. Tissues were collected and stained at 1, 2, and 24 hours post injection and was compared to untreated control animal were no human AAT protein was expressed. (b) DAB staining changes were compared between time points (Kruskal-Wallis test, median with interquartile range). (c) RT-qPCR was used to confirm the delivery of AAT encoding mRNA into liver tissue, where AAT signal passed threshold at 27 cycles and no signal was detected in untreated samples.
