Production of recombinant albumin by a herd of cloned transgenic cattle.
Purified plasma derived human albumin has been available as a therapeutic product since World War II. However, cost effective recombinant production of albumin has been challenging due to the amount needed and the complex folding pattern of the protein. In an effort to provide an abundant source of recombinant albumin, a herd of transgenic cows expressing high levels of rhA in their milk was generated. Expression cassettes efficiently targeting the secretion of human albumin to the lactating mammary gland were obtained and tested in transgenic mice. A high expressing transgene was transfected in primary bovine cell lines to produce karyoplasts for use in a somatic cell nuclear transfer program. Founder transgenic cows were produced from four independent cell lines. Expression levels varying from 1-2 g/l to more than 40 g/l of correctly folded albumin were observed. The animals expressing the highest levels of rhA exhibited shortened lactation whereas cows yielding 1-2 g/l had normal milk production. This herd of transgenic cattle is an easily scalable and well characterized source of rhA for biomedical uses.
Echelard
Yann
Y
GTC Biotherapeutics, Inc., Framingham, MA 01701-9322, USA. yann.echelard@gtc-bio.com
Williams
Jennifer L
JL
Destrempes
Margaret M
MM
Koster
Julie A
JA
Overton
Susan A
SA
Pollock
Daniel P
DP
Rapiejko
Karen T
KT
Behboodi
Esmail
E
Masiello
Nicholas C
NC
Gavin
William G
WG
Pommer
Jerry
J
Van Patten
Scott M
SM
Faber
David C
DC
Cibelli
Jose B
JB
Meade
Harry M
HM
D000418:Albumins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification*; D000818:Animals; D030801:Animals, Genetically Modified; D002417:Cattle; D002478:Cells, Cultured; D019976:Cloning, Organism; D005260:Female; D006801:Humans; D007774:Lactation; D051379:Mice; D008892:Milk / Q000378:metabolism*; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification
D000418:Albumins; D011993:Recombinant Fusion Proteins