Efficient stabilization of recombinant human coagulation factor VIII in the milk of transgenic mice using hFVIII and vWF co-expression vector transduction

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• 作者：Xiaoye Ren ; Xiuli Gong ; Qin Cai ; Xinbing Guo ; Miao Xu ; Zhaorui Ren…
• 关键词：Biological activity ; Human coagulation factor VIII ; Transgenic mammary gland bioreactor ; Transgenic mice ; von Willebrand factor
• 刊名：Biotechnology Letters
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：37
• 期：6
• 页码：1187-1194
• 全文大小：3,358 KB
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• 作者单位：Xiaoye Ren (1)
  Xiuli Gong (1)
  Qin Cai (1) (2)
  Xinbing Guo (1) (2)
  Miao Xu (1) (2)
  Zhaorui Ren (1) (2)
  Yitao Zeng (1) (2) (3)
  
  1. Shanghai Institute of Medical Genetics, Children’s Hospital of Shanghai, Shanghai Jiao Tong University School of Medicine, Shanghai, 200040, China
  2. Key Lab of Medical Embryo Molecular Biology, Ministry of Health, and Shanghai Lab of Embryo and Reproduction Engineering, Shanghai, 200040, China
  3. Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Microbiology
  Biotechnology
  Applied Microbiology
  Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-6776

文摘

Objectives To investigate the reasons for the instability of human coagulation factor FVIII (hFVIII) in milk which is an intractable obstacle during the hFVIII production by a transgenic mammary gland bioreactor. Results We constructed P1A3-hFVIIIBDD and P1A3-hFVIIIBDD-IRES-vWF co-expression cassettes for generating transgenic mice. P1A3-hFVIII/CMV-vWF double heterozygotes were also prepared by mating P1A3-hFVIIIBDD with CMV-vWF mice. hFVIII bioactivity in milk was determined under different storage conditions. The half-life (in vitro) of hFVIII bioactivity in P1A3-hFVIIIBDD-IRES-vWF mice was significantly longer than P1A3-hFVIIIBDD mice [77?±?4.9 vs. 44?±?2.6?h at 4?°C, 32.5?±?5 vs. 19.7?±?0.6?h at room temperature and 7.4?±?1.4 vs. 3.4?±?0.6 at 37?°C, respectively (P?<?0.05)]. The half-life (in vitro) of hFVIII bioactivity in milk of double heterozygotes was similar to P1A3-hFVIIIBDD-IRES-vWF ones, demonstrating that the vWF transgene expression in hFVIII transgenic mice can efficiently improve the stabilization of hFVIII bioactivity in milk. Conclusion We provide a new approach of P1A3-hFVIIIBDD-IRES-vWF co-expression to generate more stable hFVIII in transgenic milk with rapid and low cost as well as valuable information for producing pharmaceutical proteins by transgenic mammary gland bioreactor.