The landmark study by Manno et al. [37] published in Nature Medicine stands out with 1839 citations pioneering the field by demonstrating the successful transduction of the human liver with an AAV vector expressing factor IX (FIX) in patients with severe hemophilia B. Building on this, Nathwani et al. [38, 39] used a self-complementary AAV vector to achieve more durable and clinically meaningful factor IX levels, significantly reducing bleeding rates and factor usage. The gene discussed is F9; the disease is hemophilia B.