High Level Expression of Active Human Alpha-1-Antitrypsin in the Milk of Transgenic Sheep

We describe the generation of five sheep transgenic for a fusion of the ovine -lactoglobulin gene promoter to the human ₁-antitrypsin (h₁AT) genomic sequences. Four of these animals are female and one male. Analysis of the expression of h₁AT in the milk of three of these females shows that all express the human protein at levels greater than 1 gram per liter. In one case initial levels exceeded 60 grams per liter and stabilized at approximately 35 grams per liter as lactation progressed. Human ₁AT purified from the milk of these animals appears to be fully N-glycosylated and has a biological activity indistinguishable from human plasma-derived material.

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