Figure 5.

Gene expression and blood human markers

(A) OTC gene expression in livers humanized with unedited (red) or edited (blue) OTCD cells presented as percentage of mean OTC expression in humanized livers with OTCP cells (gray). Averages and errors are shown as medians and interquartile ranges. Unedited OTCD mice n = 9. Edited OTCD mice n = 15. OTCP mice n = 15. (B–F) Gene expression analysis of humanized livers that received either unedited (red) or edited (blue) OTCD cells. Expression of mature liver genes was assessed, including urea cycle genes (B), liver-secreted proteins and transcription factors (C), phase I (D), and phase II (E) genes, as well as transporters (F). Unedited OTCD mice n = 9. Edited OTCD mice n = 15. (G) Ratio of circulating human alpha-1-antitrypsin (A1AT) to albumin were measured in the blood of mice repopulated with unedited (red) or edited (blue) OTCD cells or OTCP (gray) cells. Unedited OTCD n = 13 measurements from 6 mice. Edited OTCD n = 26 measurements from 14 mice, OTCP n = 18 measurements from 11 mice at different levels of repopulation. Data are shown as medians and interquartile ranges. Statistical analysis was performed using Kruskal-Wallis ANOVA and Dunn’s multiple comparison tests. Unedited OTCD versus edited OTCD, p = 0.1405; unedited OTCD versus OTCP, p > 0.9999; edited OTCD versus OTCP, p = 0.4967.