CRISPR/Cas9-mediated knockin of human factor IX into swine factor IX locus effectively alleviates bleeding in hemophilia B pigs
| Autor: | Xinwei Zhang, Xiaohuan Peng, Tingting Yu, Xue Chen, Biao Yu, Lingyu Wang, Hongsheng Ouyang, Xiaodong Zou, Daxin Pang, Beiying An, Jiahuan Chen, He Wang, Hongming Yuan, Xiaochun Tang, Qiangbing Yang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Swine Transgene Hemorrhage Locus (genetics) Disease 030204 cardiovascular system & hematology Hemophilia A Hemophilia B Article Factor IX 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Animals Humans CRISPR Joint bleeding Pathological 030304 developmental biology 0303 health sciences Bleeding episodes business.industry Hematology Immunology CRISPR-Cas Systems business medicine.drug |
| Zdroj: | Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | Hemophilia 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. |
| Databáze: | OpenAIRE |
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