Fig. 2: DDC-induced biliary fibrosis negatively affects both LV and AAV vector transduction.
From: Liver fibrosis negatively impacts in vivo gene transfer to murine hepatocytes
a Histological image of liver section from mice (n = 10) fed with a DDC-supplemented diet for 5 weeks (bar = 300 µm). Picrosirius red staining. b Schematics of experimental design (green bar indicates DDC diet) created with BioRender (https://BioRender.com/k46g488). LV.hFIX 5 × 1010 TU/kg. LV.mCherry 3.5 × 1010 TU/kg. AAV.hFIX 2 × 1011 vg/kg. AAV.mCherry 1 × 1011 vg/kg. c Individual values with mean of hFIX concentration in the plasma. (Mann–Whitney test at the last time point). Gray and green symbols indicate mice treated with LV only (n = 8) or with DDC and LV (n = 8), respectively. d Individual values and mean ± SEM of percentage (%) of mCherry-positive liver area over the total area analyzed (Mann–Whitney test). Gray and green symbols indicate mice treated with LV only (n = 8) or with DDC and LV (n = 8), respectively. e Individual values with mean of hFIX concentration in the plasma. Orange symbols indicate female mice treated with AAV only (n = 4), red symbols indicate female mice treated with DDC and LV (n = 4), light blue symbols indicate male mice treated with AAV only (n = 3), blue symbols indicate male mice treated with DDC and LV (n = 4). f Individual values and mean ± SEM of percentage (%) of mCherry-positive liver area over the total area analyzed. AAV F and AAV M are the same data displayed in Fig. 1f, shown here for comparison. Orange symbols indicate female mice treated with AAV only (n = 4), red symbols indicate female mice treated with DDC and LV (n = 4), light blue symbols indicate male mice treated with AAV only (n = 4), blue symbols indicate male mice treated with DDC and LV (n = 4). g, h Individual values with mean ± SEM of hFIX concentration at the last time point analyzed (g row data displayed in (e)) or % of mCherry-positive liver area (h row data displayed in (f)) expressed as fold on the mean of each respective control group (Mann–Whitney test). Brown and purple symbols indicate mice treated with AAV only (for hFIX n = 7, for mCherry n = 8) or with DDC and AAV (n = 8), respectively. Source data are provided as a Source Data file.
