May 1 /PRNewswire/ -- Scientists from Athersys, a functional genomics and biopharmaceutical company, reported in a paper published today on a technology that can dramatically accelerate the pace of research in the field of functional genomics.
The May 2001 issue of ``Nature Biotechnology'' describes the technology, known as RAGE (an abbreviation for Random Activation of Gene Expression). RAGE enables rapid identification of genes associated with particular biological characteristics, as well as the discovery of novel proteins that are rarely expressed and difficult to find using conventional research techniques. In addition, the paper illustrates how RAGE can be used to produce proteins encoded by those genes, including many proteins that are difficult to obtain in quantity by traditional means.
``Now that the human genome has been sequenced, increasing attention is being placed on producing protein from every human gene, thereby allowing proteins to be tested for function,'' commented John Harrington, the study's lead author and chief scientific officer at Athersys. ``Using conventional protein production methods, every gene must first be cloned, isolated, and reintroduced into a cell to produce meaningful amounts of protein, a process that will take years to complete for all genes. The RAGE technology, on the other hand, can be used today to produce large quantities of proteins, on a genome-wide basis, without cloning individual genes. We believe this gives us a tremendous advantage in the race to understand protein function.''
Using RAGE, collections of otherwise identical cells are altered such that a single gene is randomly activated, or turned on, causing it to produce the protein encoded by the gene. In order to randomly activate each gene, researchers at Athersys treat the cells to create a temporary breakage event within one of the chromosomes contained in the cell. At the site of the chromosomal breakage, which could occur anywhere in the genome, a powerful genetic ``on switch'' is inserted. The on switch causes activation of a gene, if one happens to be located nearby, and also allows researchers to ``tag'' the gene so that it may be rapidly identified. As described in the Nature Biotechnology paper, by repeating this process with thousands or even millions of cells, researchers at Athersys create a library of cells that produce virtually every protein encoded in the human genome.
Two of the biggest challenges in biological research are how to produce meaningful quantities of rarely expressed proteins, which may be relevant as drug targets or as potential therapeutics, and how to correlate expression of a particular protein with a specific biological characteristic. Using the RAGE technology, scientists at Athersys have shown that they can create comprehensive protein expression libraries and quickly identify randomly activated genes that cause a specific biological trait.
In one experiment described in the study, Athersys scientists created a RAGE library and then looked for expression of genes that are typically ``silent''. In other words, the proteins those genes encode aren't normally produced in the cells used to make the RAGE library. For each gene in that set, the researchers were able to find at least one cell in the library that was producing the corresponding protein, indicating that the gene had been successfully activated in that cell.
The variety of proteins produced -- even rare or tightly regulated proteins -- is independent of the cell type used to make a RAGE library. Moreover, those proteins are produced at consistent levels and in substantial quantities. These properties make RAGE valuable in a number of applications, the authors write. A cell producing a protein of interest, for example one whose activity noticeably changes the behavior of the cell, can be pulled out of the library quickly and efficiently and used for further studies.
``We have taken the RAGE technology well beyond its applications in gene discovery into the realm of high throughput proteomics,'' said Dr. Gil Van Bokkelen, president and chief executive officer of Athersys. ``RAGE is a powerful technology that enables the efficient and direct correlation of functional characteristics, or phenotype, with the expression of a specific protein. We are using this technology to identify proteins involved in many clinically relevant areas.''
Athersys is a functional genomics and biopharmaceutical company engaged in the study of protein function and the development and application of novel research tools and therapeutic products. The Company's RAGE (Random Activation of Gene Expression)(TM) technology platform is a novel gene expression system that provides the unique ability to produce protein from virtually every gene in the human genome, without requiring the cloning of individual genes or use of cDNA libraries. RAGE greatly accelerates the identification and validation of novel drug targets by enabling the direct correlation of a disease process or characteristic with expression of a specific protein. As a result, RAGE has powerful applications in functional genomics; the generation of validated drug targets; the development of protein therapies; and gene discovery. Athersys is developing novel therapeutic products based on its proprietary technologies, through partnerships and internal research and development programs. This press release and further information on Athersys, Inc. can be found on the World Wide Web at: athersys.com.
The article ``Creation of Genome-Wide Protein Expression Libraries Using Random Activation of Gene Expression,'' can be found on page 440 in the May issue of Nature Biotechnology. |
