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Transgenic pigs produce functional human factor VIII in milk

Nature Biotechnology volume 15, pages 971–975 (1997)Cite this article

Abstract

Deficiency or abnormality of coagulation factor VIII (FVIII) causes a bleeding disorder called hemophilia A. Treatment involves FVIII concentrates prepared from pooled human plasma or recombinant FVIII (rFVIII) prepared from mammalian cell culture. The cost of highly purified FVIII or rFVIII is a major factor in hemophilia therapy and restricts prophylaxis. We have sought to generate a new source of rFVIII by targeting expression of the human FVIII cDNA to the mammary gland of transgenic pigs using the regulatory sequences of the mouse whey acidic protein gene. The identity of processed heterodimeric rFVIII was confirmed using specific antibodies, by thrombin digestion and activity assays. The secretion of as much as 2.7 μg/ml of rFVIII in milk was over tenfold higher than in normal plasma. Up to 0.62 U/ml of rFVIII was detected in an assay in which rFVIII restored normal clotting activity to FVIII-deficient human plasma.

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Author information

Authors and Affiliations

  1. Plasma Derivatives, Holland Laboratory, 15601 Crabbs Branch Way, Rockville, MD, 20855

    Rekha K. Paleyanda & Timothy K. Lee

  2. Coagulation Proteins Departments, Holland Laboratory, 15601 Crabbs Branch Way, Rockville, MD, 20855

    Dorothea H. Scandella & Leon W. Hoyer

  3. Chemical Engineering Virginia Polytechnic and State University, Blacksburg, VA, 24061

    William H. Velander

  4. Dairy Science Departments, Virginia Polytechnic and State University, Blacksburg, VA, 24061

    Francis C. Gwazdauskas & James W. Knight

  5. Departments of Medicine, Genetics, and Biochemistry, George Washington University, Washington, DC20037

    Leon W. Hoyer, William N. Drohan & Henryk Lubon

Authors
  1. Rekha K. Paleyanda
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  2. William H. Velander
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  3. Timothy K. Lee
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  4. Dorothea H. Scandella
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  6. James W. Knight
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  7. Leon W. Hoyer
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  8. William N. Drohan
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  9. Henryk Lubon
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Correspondence to Henryk Lubon.

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Paleyanda, R., Velander, W., Lee, T. et al. Transgenic pigs produce functional human factor VIII in milk. Nat Biotechnol 15, 971–975 (1997). https://doi.org/10.1038/nbt1097-971

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  • DOI: https://doi.org/10.1038/nbt1097-971

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