ABSTRACT
Many therapeutic proteins are derived either from human plasma by fractionation or from recombinant systems such as large-scale cell culture. Problems exist with both approaches. Large-scale culture of bacteria, yeast and mammalian cells can produce high yields of recombinant protein. However, such processes may be hindered by cost and/or the ability of the chosen system to correctly post-translationally modify the product. Blood fractionation guarantees product quality but suffers from concerns over safety, particularly with viral contamination. In several cases, neither approach can economically meet world demand for product, particularly when this is estimated in metric tonnes. Clearly, an alternative system that could produce large quantities of usable recombinant product in a cost effective manner would be attractive. Livestock can now be genetically modified to secrete recombinant proteins in their milk. By virtue of being produced by mammalian cells in vivo, such products are expected to be processed in a similar manner to proteins produced in humans. The mammary gland has an impressive capacity for protein synthesis and milk can be easily harvested. This offers the possibility of producing extremely large quantities of recombinant products by simply breeding more transgenic animals. To date, high levels of expression of a number of proteins have been achieved, although none are currently in use in the clinic. The first products from this novel approach are rapidly nearing the point where companies will seek regulatory approval for their evaluation in clinical trials. Indeed, the first two products of this new technology, recombinant alpha-1-antitrypsin and anti-thrombin III are currently in clinical trials.
