Transgenic bioreactors.
1. Although many human therapeutic proteins are currently produced in microbial fermentors using recombinant DNA techniques, it is obvious that microbial processing is not suitable for a large number of bioactive proteins owing to the inability of bacteria to carry out postsynthetic modification reactions required for full biological activity. 2. This disadvantage does not apply to animal cell bioreactors that can generate biologically fully active entities, yet the use of large-scale animal cell cultures for production purposes is prohibitively expensive. 3. With the advent of transgenic technology, the production of valuable human pharmaceuticals in large farm animals (pig, sheep, goat and dairy cattle) has become more and more attractive as a high-quantity, low-cost alternative. By employing targeted gene transfer, e.g. using mammary gland-specific regulatory sequences fused with the desired production genes, it is possible to govern the expression to occur exclusively in the mammary gland and hence the gene product is being ultimately secreted in the milk. 4. While reviewing the remarkable progress in this field that has even led to commercial exploitations, we will outline in somewhat greater detail our strategy for the use of dairy cattle as a bioreactor for valuable proteins of pharmaceutical interest.
Jänne
J
J
Department of Biochemistry & Biotechnology, University of Kuopio, Finland.
Hyttinen
J M
JM
Peura
T
T
Tolvanen
M
M
Alhonen
L
L
Sinervirta
R
R
Halmekytö
M
M
D000818:Animals; D000829:Animals, Domestic / Q000235:genetics*; D030801:Animals, Genetically Modified; D002417:Cattle / Q000235:genetics*; D002478:Cells, Cultured; D004274:DNA, Recombinant / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis*
D004274:DNA, Recombinant; D011994:Recombinant Proteins