Fig. 5: FDC2 displays superior efficacy compared to unconjugated ASO2 in HSA^LR mice.

HSA^LR mice were injected IV with vehicle (black bars/circles), 10 or 20 mg/kg unconjugated ASO2 (red bars/circles), or 10 or 20 mg/kg ASO-equivalent doses of FDC2 (blue bars/circles) and sacrificed 28 days later. a ACTA1 RNA expression measured by RT-qPCR of total RNA from quadriceps (top) or gastrocnemius (bottom) using Gtf2b as the reference gene. Expression in each muscle was normalized to ACTA1 expression in the corresponding muscle of mice injected with vehicle. Data are means + SD; data were analyzed by one-way ANOVA followed by uncorrected Fisher’s LSD test, statistically significant differences from vehicle are indicated with exact P values. Each circle represents an individual mouse. b Overall splicing derangement calculated using murine DM splicing index, horizontal lines are means ± SD, data were analyzed by one-way ANOVA followed by uncorrected Fisher’s LSD test, statistically significant differences from vehicle are indicated with exact P values. Each circle represents an individual mouse. WT splicing data (green line) previously published²⁹. c Grading of EMG myotonic discharges. Data are means + SEM; data were analyzed by Kruskal–Wallis test with Dunn’s multiple comparisons test, statistically significant differences from vehicle are indicated with exact P values. Each circle represents an individual mouse.