Analysis of the N-glycans of recombinant human Factor IX purified from transgenic pig milk

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Glycosylation of recombinant proteins is of particular importance because it can play significant roles in the clinical properties of the glycoprotein. In this work, the N-glycan structures of recombinant human Factor IX (tg-FIX) produced in the transgenic pig mammary gland were determined. The majority of the N-glycans of transgenic pig-derived Factor IX (tg-FIX) are complex, bi-antennary with one or two terminal N -acetylneuraminic acid (Neu5Ac) moieties. We also found that the N-glycan structures of tg-FIX produced in the porcine mammary epithelial cells differed with respect to N-glycans from glycoproteins produced in other porcine tissues. tg-FIX contains no detectable Neu5Gc, the sialic acid commonly found in porcine glycoproteins produced in other tissues. Additionally, we were unable to detect glycans in tg-FIX that have a terminal Galα(1,3)Gal disaccharide sequence, which is strongly antigenic in humans. The N-glycan structures of tg-FIX are also compared to the published N-glycan structures of recombinant human glycoproteins produced in other transgenic animal species. While tg-FIX contains only complex structures, antithrombin III (goat), C1 inhibitor (rabbit), and lactoferrin (cow) have both high mannose and complex structures. Collectively, these data represent a beginning point for the future investigation of species-specific and tissue/cell-specific differences in N-glycan structures among animals used for transgenic animal bioreactors. The Author 2008. Published by Oxford University Press. All rights reserved.

Original languageEnglish (US)
Pages (from-to)526-539
Number of pages14
JournalGlycobiology
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2008

Fingerprint

Factor IX
Human engineering
Polysaccharides
Milk
Swine
Glycoproteins
Animals
N-Acetylneuraminic Acid
Tissue
Genetically Modified Animals
Glycosylation
Lactoferrin
Antithrombin III
Disaccharides
Mannose
Bioreactors
Recombinant Proteins
Animal Structures
Human Mammary Glands
Goats

Keywords

  • Factor IX
  • Glycoprotein
  • Glycosylation
  • Mammary gland
  • Transgenic animal

ASJC Scopus subject areas

  • Biochemistry

Cite this

Analysis of the N-glycans of recombinant human Factor IX purified from transgenic pig milk. / Gil, Geun Cheol; Velander, William H; Van Cott, Kevin.

In: Glycobiology, Vol. 18, No. 7, 01.07.2008, p. 526-539.

Research output: Contribution to journalArticle

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