Improving on Nature: James Travis' Work on Recombinant Human {alpha}1-Proteinase Inhibitor [Molecular Bases of Disease]

In 1985, when recombinant DNA technology was still in its infancy, James Travis at the University of Georgia and colleagues developed a nonoxidizable form of a protein critical for preventing emphysema. Emphysema is an obstructive lung disease caused by progressive destruction of the lung tissue. The researchers synthesized the natural and variant forms of the protein through a partnership with the biotechnology firm Chiron and then tested it in rabbits to see if it could be used to supplement the protein in patients. They described their results in a Journal of Biological Chemistry (JBC) paper in 1985, which is now considered to be a JBC Classic.jbc;292/1/80/FU1F1FU1Measurement of the half-life of α1-proteinase inhibitor variants in rabbits.“This paper showed that you could express this protein in very high yields in yeast—higher than had ever been shown before,” says Steven Olson, a vascular biologist at the University of Illinois at Chicago. “It was one of the first demonstrations of the ability to tailor-make therapeutics.”Neutrophil elastase is a protein-degrading enzyme that is important for tissue remodeling in the lung. A protein known as human α1-proteinase inhibitor prevents the elastase from destroying everything in sight. “If the proteinase inhibitor is not sitting in the jaws of the elastase,” says Fred Guengerich, a biochemist at Vanderbilt University and the JBC Deputy Editor, “the elastase will just go around chewing holes in your lung.”But some people are born with a double genetic mutation. Their α1-proteinase inhibitor won't be properly folded, which is essential for the proper functioning...

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