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• W2023159885 abstract "The development of inhibitory antibodies directed against factor VIII (fVIII) remains the most significant clinical complication associated with the treatment of hemophilia A. Recently, we demonstrated that transplantation of genetically modified hematopoietic stem cells containing a high-expression porcine fVIII transgene promoted sustained high-level fVIII expression in naïve hemophilia A mice. In the current study, a similar gene transfer strategy was tested in hemophilia A mice harboring clinically significant anti-human factor VIII (anti-hfVIII) inhibitory antibody titers. Although the majority of mice contained circulating antibodies that cross-reacted with and inhibited porcine fVIII activity, transplantation of genetically modified hematopoietic stem cells containing a porcine fVIII transgene into myeloablated hemophilia A mice induced high-level fVIII activity. Furthermore, anti-hfVIII antibody titers steadily declined throughout the course of the study. However, non-myeloablative transplantation conditioning resulted in only partial success. No correlation between pre-transplantation antibody titers and post-transplantation fVIII activity levels or donor cell engraftment was observed. These data suggest that hematopoietic stem cell transplantation-based gene therapy incorporating a high-expression porcine fVIII transgene can be utilized successfully to treat hemophilia A patients harboring anti-hfVIII inhibitors." @default.
• W2023159885 created "2016-06-24" @default.
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• W2023159885 date "2007-06-01" @default.
• W2023159885 modified "2023-10-15" @default.
• W2023159885 title "Hematopoietic Stem Cells Encoding Porcine Factor VIII Induce Pro-coagulant Activity in Hemophilia A Mice with Pre-existing Factor VIII Immunity" @default.
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• W2023159885 doi "https://doi.org/10.1038/sj.mt.6300146" @default.
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