NEW YORK, May 1 – Athersys scientists reported on uses of their Random Activation of Gene Expression technology in a paper published Tuesday in the May 2001 issue of Nature Biotechnology .
The paper, “Creation of Genome-Wide Protein Expression Libraries Using Random Activation of Gene Expression,” detailed the application of RAGE to create genome-wide protein expression libraries, and produce proteins from genes associated with known biological characteristics.
In one experiment, researchers created a protein expression library and then searched for expression of genes not normally encoded in the cells used to make the library, explained Athersys. Researchers found at least one cell in the library that was producing the corresponding protein, leading the scientists to conclude that the gene had been successfully activated in that cell.
“RAGE libraries containing only 5 x 10 6 individual clones were found to express every gene tested, including genes that are normally silent in the parent cell line,” the study authors reported. “Endogenous genes were activated at similar frequencies and expressed at similar levels within RAGE libraries created from multiple human cell lines, demonstrating that RAGE libraries are inherently normalized.”
In the experiment, pools of RAGE clones were used to isolate 19,547 human gene clusters. Of those, the researchers reported that approximately 53 percent were novel when tested against public EST and cDNA. The authors concluded that isolation of individual clones demonstrated that the “activated endogenous genes can be expressed at high levels to produce biologically active proteins.”
This RAGE technology offers advantages over traditional protein production methods, according to John Harrington, the study’s lead author and chief scientific officer at Athersys. While traditional methods require cloning and isolation of every individual gene, then reintroduction into a cell to produce the gene’s corresponding protein, RAGE “can be used today to produce large quantities of proteins, on a genome-wide basis, without cloning individual genes,” Harrington said in a statement. “We believe this gives us a tremendous advantage in the race to understand protein function."Athersys has signed deals with Bristol-Myers Squibb, Covance, and Elan pharmaceuticals to use its RAGE technology in therapeutic discovery.