Human Plasma Proteins from Transgenic Animal Bioreactors

R. K. Paleyanda, W. H. Velander, T. K. Lee, R. Drews, F. C. Gwazdauskas, J. W. Knight, W. N. Drohan, H. Lubon

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We have evaluated the transgenic animal bioreactor (TAB) system for the production of human Protein C (HPC), an anticoagulant plasma protein. Mouse whey acidic protein (mWAP) gene regulatory sequences targeted expression of mWAP/HPC hybrid genes to the mammary gland of transgenic mice and pigs. The transgenes were stably transmitted through several generations and expression did not adversely affect the health of animals. We purified recombinant HPC from milk which was structurally and enzymatically similar to the human protein, demonstrating the potential of TABs for the production of plasma proteins. The active fraction was found to be only a part of the total protein secreted. At mg/mL levels of secretion, modifications like proteolytic maturation and γ-carboxylation became limiting factors in the production of functional protein. We have proposed and shown that these limitations may be overcome by engineering the posttranslational protein modification capacity of selected organs of the TAB.

Original languageEnglish (US)
Pages (from-to)205-217
Number of pages13
JournalACS Symposium Series
Volume647
StatePublished - Dec 1 1996

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Plasma (human)
Bioreactors
Blood Proteins
Animals
Protein C
Proteins
Genes
Carboxylation
Anticoagulants
Health
Plasmas
whey acidic proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Paleyanda, R. K., Velander, W. H., Lee, T. K., Drews, R., Gwazdauskas, F. C., Knight, J. W., ... Lubon, H. (1996). Human Plasma Proteins from Transgenic Animal Bioreactors. ACS Symposium Series, 647, 205-217.

Human Plasma Proteins from Transgenic Animal Bioreactors. / Paleyanda, R. K.; Velander, W. H.; Lee, T. K.; Drews, R.; Gwazdauskas, F. C.; Knight, J. W.; Drohan, W. N.; Lubon, H.

In: ACS Symposium Series, Vol. 647, 01.12.1996, p. 205-217.

Research output: Contribution to journalArticle

Paleyanda, RK, Velander, WH, Lee, TK, Drews, R, Gwazdauskas, FC, Knight, JW, Drohan, WN & Lubon, H 1996, 'Human Plasma Proteins from Transgenic Animal Bioreactors', ACS Symposium Series, vol. 647, pp. 205-217.
Paleyanda RK, Velander WH, Lee TK, Drews R, Gwazdauskas FC, Knight JW et al. Human Plasma Proteins from Transgenic Animal Bioreactors. ACS Symposium Series. 1996 Dec 1;647:205-217.
Paleyanda, R. K. ; Velander, W. H. ; Lee, T. K. ; Drews, R. ; Gwazdauskas, F. C. ; Knight, J. W. ; Drohan, W. N. ; Lubon, H. / Human Plasma Proteins from Transgenic Animal Bioreactors. In: ACS Symposium Series. 1996 ; Vol. 647. pp. 205-217.
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