Could Lentivirus Overcome the AAV Gene-Therapy Challenges in Hemophilia A?

Despite the unprecedented evolution of new replacement and nonreplacement therapies, many unmet needs remain with respect to the treatment of severe hemophilia A. 1 These unmet needs include preventing factor VIII–induced immunogenicity, providing consistent hemostatic protection during administration of replacement therapies, ensuring lifelong administration, and preventing musculoskeletal deterioration that occurs despite replacement and nonreplacement therapies. 2 Gene transfer with the use of adeno-associated virus (AAV) has evolved to address these unmet needs. To date, valoctocogene roxaparvovec, which delivers a functional B-domain–deleted F8 transgene, remains the only gene therapy licensed for the treatment of severe hemophilia A. 3-5 Challenges of AAV-mediated gene therapy include . . .