News Article

Novel Proteomic Arrays of In Vitro Expressed Proteins for Autoimmune Disease
Date: Mar 02, 2010
Source: NIH Success Stories ( click here to go to the source)

Featured firm in this article: Ambergen Inc of Watertown, MA



Technology Developed:
A new approach to proteomics has been developed by AmberGen, Inc. under this project based on a suite of new technologies including: a) a novel method of printing protein arrays based on photocleavage-transfer of the proteins directly from beads onto surfaces (termed PC-PRINT), b) methods for production of very large scale proteomic bead libraries (termed BS-LIVE-PRO) and c) a proprietary new solid-phase "two-tag" ELISA immunoassay (termed T2-ELISA). The overall approach reflects advances made during the project in cell-free protein synthesis, photocleavage mediated protein purification and multiplexing on beads to facilitate the production of various forms of human protein "arrays". In initial work based in part on this new technology, we have successfully identified two novel autoantigen biomarkers for the autoimmune liver disease primary biliary cirrhosis (PBC).

Uses of Technology/Products/Service:
The technology developed under this project will accelerate the pace of research in a variety of fields involving proteomics (the global study of gene products; i.e. proteins) as well as leading to the discovery of new disease-associated markers (biomarkers), especially for the diagnosis of autoimmune diseases. BS-LIVE-PRO provides the means to inexpensively and quickly produce a "proteome-in-a-bottle", a liquid suspension consisting of millions of individual microscopic beads, each bead having attached one of the tens to hundreds of thousands of proteins that make up the human proteome (the total complement of gene products; i.e. proteins). Importantly, this proteome-in-a-bottle can be randomly arrayed in one quick step onto a microscope slide or the proteins from each bead printed (PC-PRINT) as individual microscopic spots for subsequent characterization. Since proteins are the primary functional components of cells, the proteome-in-a-bottle is immensely useful for scientists to study how each protein functions and interacts with other cellular components in normal and malfunctioning (diseased) cells. One promising use is the discovery of biomarkers which if present in blood signal the presence of specific diseases. In the case of autoimmune diseases, the biomarkers are often freely circulating antibodies which are produced in response to a particular protein(s) that functions as an autoantigen(s). T2-ELISA, which also is based on creating proteins in a bottle, offers significant improvements in the rapid and robust clinical validation of these newly discovered biomarkers. Using T2-ELISA, two new biomarkers discovered by AmberGen for the autoimmune liver disease primary biliary cirrhosis (PBC), a significant cause of liver transplantation, were rapidly validated. We expect that these biomarkers will be diagnostically useful for the early detection and treatment of this debilitating disease. Another application of this new technology is to study how a specific drug which is designed to target a specific protein in the cell also interacts with all of the other proteins making up the human proteome and which often lead to serious side-effects of the drug.

Benefit to Company:
This project is leading to a suite of products and services that AmberGen will commercialize. The development of the "proteome-in-a-bottle" concept will provide researchers powerful tools to use in their biomedical research. One example is kits and reagents including libraries of proteins on beads that allows researchers to rapidly discover new autoantigens associated with specific autoimmune diseases. A second example is to enable researchers to rapidly measure protein-protein or protein-drug interactions. Efforts are currently underway to commercialize some of the technologies and diagnostic biomarkers developed/discovered under this project. Furthermore, this work has benefited AmberGen by leading to the recent publication of some of the foundation work for the developed technologies. Finally, the work has catalyzed strong collaborations between AmberGen and world-renowned research groups and hospitals in the Boston area.