A loss-of-function therapy for the ADSL deficiency. (A) A schematic presentation of the purine de novo synthesis pathway. The pathway is nearly identical among yeast, nematodes, and humans. The filled ovals mark the essential gene and the unfilled ovals show its Type II rescuing partners. (B) The worms were fed with vectors producing the double-stranded RNAs each silencing adsl-1, pacs-1, and adsl-1/pacs-1, respectively. Knockdown of pacs-1 masks well the phenotypic defects of adsl-1 knockdown. Scale bars, 1000 μm. (C) The relative growth of the F1 worms from Day 3 to Day 6 compared to a negative control wherein the worms were fed with an empty vector. The worms of adsl-1(−)/pacs-1(−) grow significantly better than those of adsl-1(−) (P < 1.4 × 10−3; Welch's t-test). Error bar, 1 SEM.
