Large scale production of recombinant human lactoferrin in the milk of transgenic cows.
The limited capacity of current bioreactors has led the biopharmaceutical industry to investigate alternative protein expression systems. The milk of transgenic cattle may provide an attractive vehicle for large-scale production of biopharmaceuticals, but there have been no reports on the characteristics of such recombinant proteins. Here we describe the production of recombinant human lactoferrin (rhLF), an iron-binding glycoprotein involved in innate host defense, at gram per liter concentrations in bovine milk. Natural hLF from human milk and rhLF had identical iron-binding and -release properties. Although natural hLF and rhLF underwent differential N-linked glycosylation, they were equally effective in three different in vivo infection models employing immunocompetent and leukocytopenic mice, and showed similar localization at sites of infection. Taken together, the results illustrate the potential of transgenic cattle in the large-scale production of biopharmaceuticals.
van Berkel
Patrick H C
PH
Pharming, Leiden, The Netherlands. p.berkel@pharming.com
Welling
Mick M
MM
Geerts
Marlieke
M
van Veen
Harry A
HA
Ravensbergen
Bep
B
Salaheddine
Mourad
M
Pauwels
Ernest K J
EK
Pieper
Frank
F
Nuijens
Jan H
JH
Nibbering
Peter H
PH
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics*; D001702:Biopharmaceutics / Q000379:methods; D001709:Biotechnology / Q000379:methods*; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D051379:Mice; D008892:Milk / Q000378:metabolism*; D009005:Monosaccharides / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry* / Q000378:metabolism*; D013997:Time Factors
D006023:Glycoproteins; D009005:Monosaccharides; D011994:Recombinant Proteins; D007501:Iron; D007781:Lactoferrin