Transgenic pigs produce functional human factor VIII in milk

Rekha K. Paleyanda, William H. Velander, Timothy K. Lee, Dorothea H. Scandella, Francis C. Gwazdauskas, James W. Knight, Leon W. Hoyer, William N. Drohan, Henryk Lubon

Research output: Contribution to journalArticle

102 Scopus citations

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 μ-g/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.

Original languageEnglish (US)
Pages (from-to)971-975
Number of pages5
JournalNature Biotechnology
Volume15
Issue number10
DOIs
StatePublished - Oct 1997

Keywords

  • Blood coagulation
  • Mammary gland
  • Transgenic animals

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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    Paleyanda, R. K., Velander, W. H., Lee, T. K., Scandella, D. H., Gwazdauskas, F. C., Knight, J. W., Hoyer, L. W., Drohan, W. N., & Lubon, H. (1997). Transgenic pigs produce functional human factor VIII in milk. Nature Biotechnology, 15(10), 971-975. https://doi.org/10.1038/nbt1097-971