Dual Vectors Expressing Murine Factor VIII Result in Sustained Correction of Hemophilia A Mice

摘要: Hemophilia A is a sex-linked disorder that results from deficiency of functional factor VIII and currently treated by protein replacement therapies. Within the past decade, gene therapy efforts have come to forefront novel therapeutics. In this work, dual-vector approach was employed in which recombinant adeno-associated viral (rAAV) vectors expressing heavy light chains murine were delivered either intramuscularly or intravenously mouse model hemophilia A. From vitro it determined coinfection with both required as heterodimerization occurs intracellularly. vivo, therapeutic levels expression achieved throughout duration study (22 weeks). Intravenous intramuscular delivery resulted maximal average 31.4 ± 6.4 29 6.5% normal levels, respectively. Western blots cryoprecipitate well immunostaining injec...