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. 2023 Jan 13;31:339–351. doi: 10.1016/j.omtn.2023.01.005

Figure 7.

Figure 7

Mouse/rat C5-siRNA/LNP treatment, but not of m/r C6-siRNA/LNP, suppresses the development of arthritis in CIA mice

(A–C) Prophylactic treatment with m/r C5-siRNA/LNP. Arthritis score (A), body weight change (B), and hemolysis (C) in CIA mice treated with PBS (n = 8), Ctrl-siRNA/LNP (n = 8), or m/r C5-siRNA/LNP (n = 8) and in normal mice (n = 4) are shown. Mice received i.v. administration of PBS, 1 mg/kg Ctrl-siRNA/LNP, or 0.1 mg/kg m/r C5-siRNA/LNP once per week from the day of the first immunization (day 0). Arthritis score was monitored from second immunization (day 21) onward, once or twice per week. (b) Body weights of mice treated with PBS, Ctrl-siRNA/LNP, or m/r C5-siRNA/LNP were expressed as a ratio of the initial body weight (day −4). (C and D) Blood samples were collected to evaluate the complement hemolytic (C) activity and MMP-3 level (D). Data are presented as the mean ± SEM. n = 4–8/group; ∗p < 0.05 and ∗∗∗∗p < 0.0001 versus PBS. (E and F) Therapeutic treatment with m/r C5-siRNA/LNP. Arthritis score (E) and body weight change (F) in CIA mice treated with PBS (n = 10), Ctrl-siRNA/LNP (n = 10), or m/r C5-siRNA/LNP (n = 7) and in normal mice (n = 4) are shown. (E) Mice with arthritis scores of 1–3 were randomly enrolled into groups and received i.v. administration of PBS, 1 mg/kg Ctrl-siRNA/LNP, or 1 mg/kg m/r C5-siRNA/LNP once per week from the day of enrollment. Arthritis score was sequentially monitored from enrollment once or twice per week. (F) Body weights of mice treated with PBS, Ctrl-siRNA/LNP, or m/r C5-siRNA/LNP were expressed as a ratio of the initial body weight (week −1). Data are presented as the mean ± SEM. n = 4–10/group; ∗∗p < 0.01 and ∗∗∗∗p < 0.0001 versus PBS. (G and H) Prophylactic treatment with m/r C6-siRNA/LNP. Arthritis score (G) and body weight change (H) in CIA mice treated with PBS (n = 6), Ctrl-siRNA/LNP (n = 6), or m/r C6-siRNA/LNP (n = 6) and in normal mice (n = 4) are shown. (F) Mice received i.v. administration of PBS, 1 mg/kg Ctrl-siRNA/LNP, or 1 mg/kg m/r C6-siRNA/LNP once per week from the day of the first immunization (day 0).