Given that TET3 expression is aberrantly elevated in the livers of patients with T2D (12) and that let-7 overexpression represses the TET3/HNF4α-P2 axis and reduces glucose production in primary hepatocytes from obese humans (Fig. 4 J–L and SI Appendix, Fig. S4 C–E), as well as the success of liver-directed gene therapy with AAV vectors in patients with hemophilia B (51, , –54), targeting the hepatic let-7/TET3/HNF4α-P2 pathway using liver-specific AAV vectors will be highly clinically relevant. Here, TET3 is linked to hemophilia B.