Therapeutic proteins are an example of high-value proteins whose biosynthesis and downstream recovery has been limited by low productivity, extreme contamination, FDA requirements and difficulties due to improper modification or deleterious altering of the protein structure by the genetically engineered production system such as tissue culture. These problems have led to an undesirable mode of treatment available to people such as hemophiliacs due to cost and limited availability of the replacement protein. A detailed understanding of the structure and activity of the protein produced by the recombinant system facilitates the engineering of recovery methods for appropriate forms of the protein of interest as well as having genetic value for the recovery of other proteins using that same expression system. Transgenic mice which express human Protein C that is biologically active have been a good model for the production of a therapeutic protein by using a mammal as a bioreactor. Protein C is an anti-clotting protein which has potential for the treatment of clotting problems associated with septic shock, heart attack, and hip replacement surgery. The distribution of Protein C products is being evaluated based upon proteolytic and biosynthetic modifications characteristic of mammary tissue expression. Proteolysis seems to effect the integrity of the Protein C produced in murine milk. Pig milk doped with Protein C has also shown this same problem. Transgenic pigs containing the same genetic information as successfully used in mice are being evaluated as a large scale bioreactor with the potential of grams of heterologous protein per day. An immunoaffinity procedure for isolation of Protein C from murine and pig milk is being developed. The future use of transgenic animal bioreactors depends upon the knowledge of the biochemical changes that are affected by the mammary tissue and milk environments.
