Atryn

Atryn, trade name of recombinant human antithrombin, an anticoagulant agent used to prevent thrombosis—the formation of a clot in a blood vessel that may block or impede the flow of blood, causing a potentially life-threatening condition. Atryn was developed by U.S.-based GTC Biotherapeutics and was the first therapeutic agent produced by using transgenic animals (animals whose genomes have been altered by the addition of a gene from another species) to gain approval for use in humans. The drug was approved by the European Commission in 2006 and by the U.S. Food and Drug Administration in 2009.

Atryn is used in patients with hereditary antithrombin deficiency, a disorder that is estimated to affect one in every 5,000 people. Antithrombin normally circulates in the blood plasma, where it binds to and inactivates certain factors involved in coagulation (the process of clot formation). People affected by antithrombin deficiency are at high risk of thrombotic events, including pulmonary embolism and deep vein thrombosis. Atryn works similarly to antithrombin and therefore serves as an effective form of replacement therapy for people with hereditary deficiency. The most common side effects associated with Atryn include headache, hemorrhage at the site of infusion, allergic reaction, and nausea.

The transgenic animals designed to produce Atryn are goats whose genomes have been altered for the secretion of human antithrombin protein in their milk. Using recombinant DNA technology, scientists were able to attach the protein-coding region of the human antithrombin gene to a segment of DNA from a goat mammary gland gene that directs the release of the gene product into milk. The resulting recombinant gene, called a transgene, was then inserted into cells grown in cell culture in a laboratory. This enabled gene activity to be evaluated and cells containing the transgene to be generated for the subsequent production of transgenic animals.

Transgenic goats for breeding and herd propagation were developed by means of cloning technology based on the process of nuclear transfer—the introduction of a cell nucleus into an egg cell that has been enucleated and thus no longer possesses a nucleus of its own. Nuclear transfer was performed by fusing the transgene-containing cells grown in culture with egg cells from female goats. The eggs were fertilized, and the resulting embryos were implanted into surrogate mothers. The first-generation founder goats were then bred to give rise to female “production” goats, which serve as the main sources of Atryn. Goats in the Atryn herd undergo regular testing for activity of the human antithrombin gene; those goats with the highest levels of gene activity and therefore the highest quantities of antithrombin production are selected for breeding. See pharming.