AbstractHemophilia B is an X-linked recessive bleeding disorder caused by abnormalities in the coagulation factor IX gene. Without prophylactic treatment, patients experience frequent spontaneous bleeding episodes. Well-characterized animal models are valuable for determining the pathobiology of the disease and testing novel therapeutic innovations. Here, we generated a porcine model of hemophilia B using a combination of CRISPR/Cas9 and somatic cell nuclear transfer. Moreover, we tested the possibility of hemophilia B therapy by gene insertion. Frequent spontaneous joint bleeding episodes that occurred in hemophilia B pigs allowed a thorough investigation of the pathological process of hemophilic arthropathy. In contrast to the hemophilia B pigs, which showed a severe bleeding tendency and joint damage, the transgenic pigs carrying human coagulation factor IX exhibited a partial improvement of bleeding. In summary, this study not only offers a translational hemophilia B model for exploring the pathological process of hemophilic arthropathy but also provides a possibility for the permanent correction of hemophilia in the future by genome editing in situ.
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Ferrata Storti Foundation, Pavia, Italy
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