Friday, October 05, 2018

Directed Evolution Via Phage Display


thescientist |  Caltech’s Frances Arnold, who advanced a technique called directed evolution to shape the function of enzymes, has received the Nobel Prize in Chemistry today (October 3). She shares the honor with George Smith, now emeritus professor of the University of Missouri, and Gregory Winter, emeritus group leader at the Medical Research Council Laboratory of Molecular Biology (LMB) in Cambridge, UK. Smith and Winter are both recognized for their work on a lab technique known as phage display in the directed evolution of new proteins—in particular, for the production of antibody therapeutics.

“I’d like to congratulate this year’s laureates for their tremendous breakthrough work in using chemistry to speed nature's own processes,” Peter Dourhout, president of the American Chemical Society, says in a statement. “The breakthroughs from these researchers enable that to occur thousands of times faster than nature to improve medicines, fuels and other products. This is truly directed evolution using chemistry.”

First reported by Smith in 1985, phage display involves the introduction of foreign DNA coding for a protein, such as an antibody, into a bacteriophage—a virus that infects bacteria. That protein is then displayed on the surface of the phage. Researchers can use these protein-displaying phages to screen for interactions with other proteins, DNA sequences, and small molecules. 

Speaking to the Associated Press this morning, Smith emphasized the role of others’ work in his achievement. “Very few research breakthroughs are novel,” he says. “Virtually all of them build on what went before. . . . That was certainly the case with my work.”

Winter, who cofounded the biotech company Cambridge Antibody Technology in 1989, developed the technique for the purpose of finding novel therapeutics. In 1993, his research group used phage display to successfully isolate fragments of human antibodies that could bind specific antigens. The genes for these fragments could be expressed in bacteria, the team reported, and could offer a “promising alternative” to mouse-based methods for the “production of antibodies against cell surface molecules.”

In 2002, adalimumab (Humira), a therapeutic produced by this approach, was approved by European and US regulators for the treatment of rheumatoid arthritis. Speaking in 2006, Winter called the approval “the sort of thing I’m most proud of.” The technique has since been used to isolate molecules against autoimmune diseases, multiple cancers, and bacteria such as Bacillus anthracis—the cause of anthrax.