Pre-clinical evaluation of an enhanced-function factor VIII variant for durable hemophilia A gene therapy in male mice

• Published in: Nature communications Vol. 15; no. 1; pp. 7193 - 14
• Main Authors: Sternberg, Anna R., Martos-Rus, Cristina, Davidson, Robert J., Liu, Xueyuan, George, Lindsey A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 38/44; 42; 631/45; 631/45/612; 64/60; 692/308; 82/80; Activated protein C; Animals; Clinical trials; Coagulation factors; Copy number; Dependovirus - genetics; Disease Models, Animal; Durability; Factor VIII - genetics; Factor VIII - metabolism; Factor VIII deficiency; Gene expression; Gene therapy; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Hemophilia; Hemophilia A - genetics; Hemophilia A - therapy; Hemostasis; Hemostatics; Humanities and Social Sciences; Humans; Inactivation; Male; Males; Mice; Mice, Inbred C57BL; multidisciplinary; Recovery of function; Science; Science (multidisciplinary)

Durable factor VIII expression that normalizes hemostasis is an unrealized goal of hemophilia A adeno-associated virus-mediated gene therapy. Trials with initially normal factor VIII activity observed unexplained year-over-year declines in expression while others reported low-level, stable expressio...