EglN siRNA activates hepatic Epo production and stimulates erythropoiesis. (A) Overview of dosing schedule and bleeds. Mice were dosed intravenously with LNPs containing an equal mixture of 3 siRNAs targeting EglN1, EglN2, and EglN3, respectively (total dose, 1 mg/kg). Mice treated with PBS or a similarly prepared LNP containing a single siRNA against firefly luciferase served as controls. (B-D) Hepatic EglN mRNA (B), hepatic Epo mRNA (C) at day 9, and serum Epo (D) levels at day 4. mRNA levels were normalized to GAPDH mRNA levels and then to the corresponding values in PBS-treated mice. (E) Hematology measurements at day 4 after first dose or day 9 after 2 doses. (F-G) Serum Epo (F) and hematocrit (G) levels in mice treated as in panel A with 2 doses of siRNA against the EglN family members or against firefly luciferase (LUC). For panels A through E, n = 5; for panels F and G, n = 3. Error bars represent 1 SD. **P < .01.