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. Author manuscript; available in PMC: 2021 Sep 1.
Published in final edited form as: Sci Transl Med. 2021 Feb 10;13(580):eabd3438. doi: 10.1126/scitranslmed.abd3438

Figure 1. Innate immune response and human factor IX expression in mice following intravenous AAV8 administration.

Figure 1.

(A) Schematic diagram of vector organization of scAAV.FIX and scAAV.FIX.io1. The io1 sequence is not expected to be transcribed or translated due to its placement in an untranslated region upstream of the promoter. (B) Innate immune response in liver assayed by qPCR 2 h after 1 × 1011 vg AAV8 administration in C57BL/6 mice. n = 6 – 7 animals per condition. (C) Innate immune response in liver assayed by qPCR 2 h after 1 × 1010 vg AAV8 administration in C57BL/6 mice. n = 4 – 5 animals per condition. (D) Innate immune response in liver assayed by qPCR 2 h after 1 × 1011 vg AAV8 administration in Tlr9−/− mice. n = 4 animals per condition. (E) Innate immune response in liver assayed by qPCR 2 h after 1 × 1011 vg AAV8 administration in Myd88−/− mice. n = 4 animals per condition. PBS injection was set to 1-fold expression for each gene. Data shown are mean ± s.e.m. per condition. * p<0.05 by two-tailed Mann-Whitney test and compared against PBS condition. ns, not significant, p>0.05. (F) F4/80+ macrophage infiltration in C57BL/6 mouse liver 2 h after 1 × 1011 vg AAV8 administration. Data shown are mean of n = 6 – 7 animals per condition. * p<0.005 by two-tailed Mann-Whitney test. Scale bar, 100 μm. (G) Human factor IX in plasma of C57BL/6 mice at indicated time points after 1 × 1011 vg AAV8 administration. n = 7 – 8 animals per condition. (H) Human factor IX in plasma of C57BL/6 mice at indicated time points after 1 × 1010 vg AAV8 administration. n = 4 animals per condition. (I) Human factor IX in plasma of Myd88−/− mice at indicated time points after 1 × 1011 vg AAV8 administration. n = 3 – 4 animals per condition. Data shown are mean ± s.d. per condition. ** p<0.005 by two-tailed Mann-Whitney test. ITR, inverted terminal repeat; TTR, transthyretin promoter; hFIX, human factor IX; bGH, bovine growth hormone poly(A) signal; TRS, terminal resolution site.