Plasma levels and therapeutic efficacy of the expressed plasma ADAMTS13 variant in mice. (A-B) The dynamic changes of plasma VWF-cleaving activity (U/mL) and antigen (μg/mL) over time (weeks), as determined by rFRETS-mVWF73 and ELISA, respectively, in mice treated with various doses of AAV8-hAAT-mdtcs. Each time point represents the mean ± SD of 5 individual mice (n = 5). Wild-type murine plasma pooled from 10 mice was used as a standard for the calibration of proteolytic activity (1 U/mL). A purified recombinant mdtcs fragment spiked into the Adamts13^−/− murine plasma was used for calibration of plasma antigen levels. (C-F) The daily platelet counts before (day 0) and after the Stx2 challenge in Adamts13^−/− mice that were pretreated with a single dose of AAV8-hAAT-lacZ (1.3 × 10¹² vg/kg) or various doses of AAV8-hAAT-mdtcs as indicated. (G) The Kaplan-Meier survival rates over 7 days in mice treated with control vector and therapeutic AAV8 vector at various doses and challenged with Stx2. A P value < .001 is considered statistically significant.