AAV liver gene therapy eradicates FIX inhibitors in a hemophilia B dog. (A) Expression of hepatocyte-restricted FIX Padua (green triangle) leads to a protolerance cytokine profile including IL-10 secretion (blue circles), which may modify the preexisting inflammatory environment including high IL-6 levels, facilitating tolerance induction of anti-FIX antibodies (red). (B) Time course of preexisting inhibitor eradication following AAV liver gene therapy in a hemophilia B dog (Wiley). The increased specific activity of FIX Padua results in high levels of FIX activity, with an activity-to-antigen ratio of ∼8. Adapted from Figures 2 and 3 in the article by Crudele et al beginning on page 1553.