However, in a subsequent phase 1/2 dose escalation trial, hemophilia B patients administered a high dose of liver-directed AAV2-fIX (2 × 1012 vg/kg) developed transient therapeutic fIX levels that correlated with adaptive immunity to AAV as well as an elevation in liver transaminases (ALT, AST) that declined following loss of fIX expression (47). Here, F9 is linked to hemophilia B.