Transgenic pigs produce functional human factor VIII in milk

Nature Biotechnology

Volumn 15, Issue 10, 1997, Pages 971-975

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

^a HOLLAND LABORATORY   (United States)

^b VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY   (United States)

^c GEORGE WASHINGTON UNIVERSITY   (United States)

Author keywords

Blood coagulation; Mammary gland; Transgenic animals

Indexed keywords

BLOOD CLOTTING FACTOR 8;

ARTICLE; BLOOD CLOTTING; HEMOPHILIA A; HUMAN; MILK LEVEL; NONHUMAN; PRIORITY JOURNAL; PROTEIN DETERMINATION; PROTEIN SYNTHESIS REGULATION; PROTEIN TARGETING; TRANSGENIC ANIMAL;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; BLOOD COAGULATION; DIMERIZATION; DNA, COMPLEMENTARY; FACTOR VIII; FEMALE; GENE EXPRESSION REGULATION; HEMOPHILIA A; HUMANS; MAMMARY GLANDS, ANIMAL; MICE; MILK; MILK PROTEINS; RECOMBINANT PROTEINS; SWINE; THROMBIN;

ANIMALIA; MAMMALIA;

EID: 0030771837     PISSN: 10870156     EISSN: 15461696     Source Type: Journal    
DOI: 10.1038/nbt1097-971     Document Type: Article

References (39)

1. Vehar, G.A., Keyt, B., Eaton, D., Rodriguez, H., O’Brien, D.P., Rotblat, F., et al. 1984. Structure of human factor VIII. Nature 312:337-342.
2. Toole, J.J., Knopf, J.L., and Wozney, J.M. 1984. Molecular cloning of a cDNA encoding human antihemophilic factor. Nature 312:342-347.
3. Wood, W.I., Gapon, D.J., Simonsen, C.C., Eaton, D.L., Gitschier, J., Keyt, B., et al. 1984. Expression of active human factor VIII from recombinant DNA clones. Nature 312:330-337.
4. Hoyer, L.W. 1993. Characterization of dysfunctional factor VIII molecules. Methods Enzymol. 222:169-176.
5. Weiss, H.J., Sussman, I.I., and Hoyer, L.W. 1977. Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand’s disease. J. Clin. Invest. 60:390-404.
6. Ehmann, W.C., Eyster, M.E., Aledort, L.M., and Goedert, J.J. 1995. Causes of death in hemophilia. Nature 378:124.
7. Gitschier, J., Wood, W.I., Goralka, T.M., Wion, K.L, Chen, E.Y., Eaton, D.H., et al. 1984. Characterization of the human factor VIII gene. Nature 312:326-330.
8. Eaton, D.L., Wood, W.I., Eaton, D., Hass, P.E., Hollingshead, P., Wion, K., Mather et al. 1986. Construction and characterization of an active factor VIII variant lacking the central one-third of the molecule. Biochem. 25:8343-8347.
9. Toole, J.J., Pittman, D.D., Orr, E.C., Murtha, P., Wasley, L.C., and Kaufman, R.J. 1986. A large region (~95 kD) of human factor VIII is dispensable for in vitro pro-coagulant activity. Proc. Natl. Acad. Sci. USA 83:5939-5942.
10. Kaufman, R.J., Wasley, L.C., and Dorner, A.J. 1988. Synthesis, processing and secretion of recombinant human factor VIII expressed in mammalian cells. J. Biol. Chem. 263:6352-6362.
11. Kaufman, R.J., Wasley, L.C., Davles, M.V., Wise, R.J., Israel, D.I., and Dorner, A.J. 1989. Effect of von Willebrand factor coexpression on the synthesis and secretion of factor VIII in Chinese hamster ovary cells. Mol. Cell Biol. 9:1233-1242.
12. Lynch, C.M., Israel, D.I., Kaufman, R.J., and Miller, A.D. 1993. Sequences in the coding region of clotting factor VIII act as dominant inhibitors of RNA accumulation and protein production. Hum. Gene Ther. 4:259-272.
13. Koeberl, D.D., Halbert, C.L, Krumm, A., and Miller, A.D. 1995. Sequences within the coding regions of clotting factor VIII and CFTR block transcriptional elongation. Hum. Gene Ther. 6:469-479.
14. Hoeben, R.C., Fallaux, F.J., Cramer, S.J., van den Wollenberg, D.J.M., van Ormondt, H., Briet, E., et al. 1995. Expression of the blood-clotting factor VIII cDNA is repressed by a transcriptional silencer located in its coding region. Blood 85:2447-2454.
15. Koedam, J.A., Meijers, J.C.M., Sixma, J.J., and Bouma, B.N. 1988. Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor. J. Clin. Invest. 82:1236-1243.
16. Lubon, H., Paleyanda, R.K., Velander, W.H., and Drohan, W.N. 1996. Blood proteins from transgenic animal bioreactors. Transfus. Med. Revs. X:131-143.
17. Campbell, S.M., Rosen, J.M., Hennighausen, L.G., Strech-Jurk, U., and Sippel, A.E. 1982. Comparison of the whey acidic protein genes of the rat and mouse. Nucleic Acids Res. 12:8685-8697.
18. Fulcher, CA. and Zimmerman, T.S. 1982. Characterization of the human factor VIII procoagulant protein with a heterologous precipitating antibody. Proc. Natl. Acad. Sci. USA 79:1648-1652.
19. Eaton, D., Rodriguez, H., and Vehar, G.A. 1986. Proteolytic processing of human factor VIII. Correlation of specific cleavages by thrombin, factor X, and activated protein C with activation and inactivation of factor VIII coagulant activity. Biochem. 25:505-512.
20. Fulcher, C.A., Roberts, J.R., and Zimmerman, T.S. 1983. Thrombin proteolysis of purified factor VIII. Correlation of activation with generation of a specific polypeptide. Blood 61:807-811.
21. Pittman, D.D. and Kaufman, R.J. 1988. Proteolytic requirements for thrombin activation of anti-hemophilic factor (factor VIII). Proc. Natl. Acad. Sci. USA 8:2429-2433.
22. Rosen, S. 1984. Assay of factor VIII:C with a chromogenic substrate. Scand. J. Haematol. 33 (suppl. 40):139-145.
23. Over, J. 1984. Methodology of the one-stage assay of factor VIII (VIII:C). Scand. J. Haematol. 41:13-24.
24. Clark, A.J., Bessos, H., Bishop, J.O., Brown, P., Harris, S., Lathe, R., et al. 1989. Expression of human anti-hemophilic factor IX in the milk of transgenic sheep. Bio/Technology 7:487-492.
25. Lee, T., Drohan, W.N., and Lubon, H. 1995. Proteolytic processing of human protein C in swine mammary gland. J. Biochem. 118:81-87.
26. Yarus, S., Greenberg, N.M., Wei, Y., Whitsett, J.A., Weaver, T.E., and Rosen, J.M. 1997. Secretion of unprocessed human surfactant protein B in the milk of transgenic mice. Transgenic Res. 6:51-57.
27. Drohan, W.N., Zhang, D.-W., Paleyanda, R.K., Chang, R., Wroble, M., Velander, W., et al. 1994. Inefficient processing of human protein C in the mouse mammary gland. Transgenic Res. 3:355-364.
28. Denman, J., Hayes, M., O’Day, C., Edmunds, T., Bartlett, C., Hirani, S., et al. 1991. Transgenic expression of a variant of human tissue-type plasminogen activator in goat milk: Purification and characterization of the recombinant enzyme. Bio/Technology 9:839-843.
29. Mikkelsen, T.R., Brandt, J., Larsen, H.J., Larsen, B.B., Poulsen, K., Ingerslev, J., et al. 1992. Tissue-specific expression in the salivary glands of transgenic mice. Nucl. Acids Res. 20:2249-2255.
30. Pittius, C.W., Hennighausen, L., Lee, E., Westphal, H., Nicol, E., Vitale, J., et al. 1988. A milk protein gene promoter directs the expression of human tissue plasminogen activator cDNA to the mammary gland in transgenic mice. Proc. Natl. Acad. Sci. USA 85:5874-5878.
31. Reddy, V.B., Vitale, J., Wei, C., Montoya-Zavala, M., Stice, S.L., Balise, J., et al. 1991. Expression of human growth hormone in the milk of transgenic mice. Animal Biotechnol. 2:15-29.
32. Günzburg, W.H., Salmons, B., Zimmermann, B., Muller, M., Erfle, V, and Brem, G. 1991. A mammary-specific promoter directs expression of growth hormone not only to the mammary gland, but also to Bergman glia cells in transgenic mice. Mol. Endocrinol. 5:123-133.
33. Wen, J., Kawamata, Y., Tojo, H., Tanaka, S., and Tachi, C. 1995. Expression of Whey acidic protein (WAP) genes in tissues other than the mammary gland in normal and transgenic mice expressing mWAP/hGH fusion gene. Mol. Reprod. Dev. 41:399-406.
34. Wall, R.J., Pursei, V.G., Shamay, A., McKnight, R.A., Pittius, C.W., and Hennighausen, L. 1991. High-level synthesis of a heterologous milk protein in the mammary glands of transgenic swine. Proc. Natl. Acad. Sci. USA .88:1696-1700.
35. Drohan, W.N., Wilkins, T.D., Latimer, E., Zhou, D., Velander, W., Lee, T.K., et al. 1994. A scalable method for the purification of recombinant human protein C from the milk of transgenic swine, pp. 501-507 in Advances in bioprocess engineering. Galindo, E. and Ramirez, O.T. (eds.) Kluwer Academic Publishers, Dordrecht, The Netherlands.
36. Velander, W.H., Johnson, J.L., Page, R.L., Russell, C.G., Subramanian, A., Wilkins, T.D., et al. 1992. High-level expression of a heterologous protein in the milk of transgenic swine using the cDNA encoding human protein C. Proc. Natl. Acad. Sci. USA 89:12003-12007.
37. Wall, R.J., Pursel, V.G., Hammer, R.E., and Brinster, R.L. 1985. Development of porcine ova that were centrifuged to permit visualization of pronuclei and nuclei. Biol. Reprod. 32:645-651.
38. Fulcher, C.A., Roberts, J.R., Holland, L.Z., and Zimmerman, T.S. 1985. Human factor VIII procoagulant protein. Monoclonal antibodies define precursor-product relationships and functional epitopes. J. Clin. Invest. 76:117-124.
39. Lubin, I.M., Healey, J.F., Scandella, D., Runge, M.S., and Lollar, P. 1994. Elimination of à major inhibitor epitope in Factor VIII. J. Biol. Chem. 269:8639-8641.