Multiplexed screening of protein expression libraries

DESCRIPTION (provided by applicant): In Phase I of this project, Trellis Bioscience, Inc. has validated a proprietary screening technology for multiplexed characterization of the secreted protein from individual live cells, enabling detection and propagation of rare favorable cells. The technology was applied to murine splenocytes and hybridomas, achieving a specificity (quality) threshold that is markedly higher than is feasible for other antibody screening technologies. The identified clones were too rare for recovery by conventional means lacking the extreme miniaturization of the Trellis approach (100,000 fold reduction). The present Phase II request for funding is to enable extension of the technology from murine hybridomas to two distinctive diversity sources: recombinant antibodies, and recombinant small peptides. Each addresses market needs not satisfied by murine hybridomas. Successful extension to recombinant antibodies will allow the recovery of human derived antibodies against infectious diseases, extending the benefits of vaccination to diseases for which a mass innoculation campaign is impractical or inappropriate. Peptides are of particular interest for targeting intracellular drug targets not amenable to antibody treatment. Extension to these uses requires a substantive increase in throughput of the screening system. Accordingly, Aim 1 is focused on increasing the multiplexing capacity of the assay and improving the efficiency and throughput of the image analysis system, while Aims 2 and 3 are focused on adapting the technology and demonstrating its capabilities in the two fields of interest. Trellis Bioscience is developing a technology that decreases the time and cost required to discover antibody therapeutics, which now represent the fastest growing segment of the pharmaceutical industry. Drugs in this class are being used to treat cancer and inflammatory diseases, as well as infectious disease. A further extension of the technology to peptide therapeutics will allow the efficient development of drugs to treat diseases that are not currently amenable to antibody based approaches.