In this study, we tested the proof of concept that genome editing-mediated knock-in of hF9 into the APOC3 gene may have applications as an advanced therapeutic option for hemophilia B. We showed that dual AAV-mediated delivery of CjCas9 and a donor template led to the efficient expression of hFIX and recovery of clotting function in hemophilia model mice. Here, APOC3 is linked to hemophilia.