Lentivirus-mediated gene therapy in a beta-thalassemia mouse model

• A novel lentiviral vector HS40-LV achieved 50% transduction efficiency in hematopoietic stem cells and stable expression in vivo. • Gene therapy with HS40-LV led to sustained increases in vector marking and β-globin-positive red blood cells, reaching 50% and 70% respectively at 10 months. • Treatment corrected hematological parameters and reduced iron deposition in spleen and liver, improving extramedullary hematopoiesis. • The study supports the feasibility of ex vivo lentiviral gene therapy for β-thalassemia, providing a foundation for clinical translation.