TRANSGENIC PIGS PRODUCE FUNCTIONAL HUMAN FACTOR-VIII IN MILK

Deficiency or abnormality of coagulation factor VIII (FVIII) causes a bleeding disorder called hemophilia A. Treatment involves FVIII concen trates prepared from pooled human plasma or recombinant FVIII (rFVIII) prepared from mammalian cell culture, The cost of highly purified FVI II or rFVIII is a major factor in hemophilia therapy and restricts pro phylaxis. We have sought to generate a new source of rFVIII by targeti ng expression of the human FVIII cDNA to the mammary gland of transgen ic pigs using the regulatory sequences of the mouse whey acidic protei n gene. The identity of processed heterodimeric rFVIII was confirmed u sing specific antibodies, by thrombin digestion and activity assays, T he secretion of as much as 2.7 mu g/ml of rFVIII in milk was over tenf old higher than in normal plasma, Up to 0.62 U/ml of rFVIII was detect ed in an assay in which rFVIII restored normal clotting activity to FV III-deficient human plasma.