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

Abstract

We describe the generation of five sheep transgenic for a fusion of the ovine β-lactoglobulin gene promoter to the human α1-antitrypsin (hα1AT) genomic sequences. Four of these animals are female and one male. Analysis of the expression of hα1AT 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 α1AT 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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