Genzyme Corp. said Monday that it has developed the firsttransgenic mouse able to produce in its milk the membraneprotein cystic fibrosis transmembrane regulator.
CFTR, the protein coded by the gene associated with cysticfibrosis, is a chloride channel that allows chloride ions to passout of cells. It normally resides on the surface membrane ofairway cells. In mutant forms, the newly made protein isunable to move to the surface membrane where it belongs, andis destroyed.
CF, which clogs the lungs with thick mucus, affects about30,000 people in the United States and occurs in one in every2,000 to 3,000 live births.
Membrane proteins have been considered very difficult tomake in large amounts, said Alan Smith, senior vice presidentof research. Such proteins include channels and pumps for thepassage of material into and out of cells, and receptors to whichhormones, growth factors and viruses bind to enter cells.Normally, membrane proteins are firmly embedded within themembrane of cells.
Currently, the only way to produce membrane proteins isthrough engineered mammalian cells, Smith told BioWorld. "Butthere seems to be a low upper limit on how much can be made-- about 100,000 to 1 million molecules per cell."
The company (NASDAQ:GENZ) said this is the first timemembrane proteins have been produced using transgenics.Genzyme hopes that transgenic animals will produce largeramounts of the proteins.
Genzyme scientists, working in collaboration with researchersat the Tufts University School of Veterinary Medicine in NorthGrafton, Mass., expressed the CFTR gene in mouse mammarytissue. Fat produced by mammary cells is surrounded by amembrane, which contains the CFTR protein. Milk fat globulesmay comprise up to 10 percent of whole milk.
The next step is to scale up to production in goats, which couldbe relatively inexpensive bioreactors for producing researchquantities of CFTR. Genzyme needs large quantities for itsenzyme-replacement therapy, which is in the research stage.The Cambridge, Mass., company plans to begin working withthe larger animals this year.
Last August, Genzyme and Tufts announced that they haddeveloped transgenic goats that secrete tissue plasminogenactivator in their milk.
Genzyme shares on Monday rose 25 cents to $56.50.
-- Karen Bernstein BioWorld Staff
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