Life-long correction of orotic aciduria and underlying OTC deficiency in adult Spfash mice. Adult male Spfash mice were injected intraperitoneally with vector doses shown to provide short-term correction (Figure 2), and urinary orotic acid levels followed up to 22 months. Liver OTC activity was also examined at 2 weeks, 12, and 18–20 months postinjection. (a) Urinary orotic acid levels in pre- and postinjection urine samples from wild-type (n = 10), untreated Spfash (n = 8), and Spfash mice injected with 5 × 1010 vg (n = 6) or 1.5 × 1011 vg (n = 4). (b) OTC enzyme activity in liver lysates from representative wild-type (n = 1–6), untreated Spfash (n = 1–6), and Spfash mice injected with 5 × 1010 vg (n = 1–5) or 1.5 × 1011 vg (n = 1–6). Error bars in a and b represent mean ± SEM. OTC, ornithine transcarbamylase; Spfash, OTC-deficient; vg, vector genome; wt, wild-type.