Runx2 takes center stage in regulating HSC expansion

FIX and FX simultaneously, facilitating formation of a ternary complex that enhances FIXa-mediated FX activation.This mechanism resembles that of emicizumab, a clinically validated FVIII-mimetic bispecific antibody used successfully in patients with severe hemophilia A. In FVIII-deficient mice, a single IV injection of AAV8-Bi8 corrected the bleeding diathesis as measured by tail vein transection.Blood loss reduction was comparable to emicizumab-treated (5 mg/kg), FVIII-treated (2.5 IU/ml), and wild-type controls.Importantly, despite being a foreign antigen, Bi8 did not elicit detectable antidrug antibodies, possibly due to hepatic immune tolerance, as observed with other therapeutic transgenes. 2