Chip-based technologies - e.g. DNA microarrays and next generation sequencing - have profoundly accelerated the pace of biomedical discovery because they are miniaturized, multiplexed, and highly scalable. By combining SpectraGenetics' FAP technology with printed reverse transfection microarrays, we intend bring these same virtues to live-cell screening against GPCRs and other receptors, which are the most prevalent targets of therapeutic drugs. The new screening system will detect and quantify the responses of many GPCRs in parallel by interrogating arrayed reverse-transfected mammalian cells that express FAP- tagged receptors. This miniaturized, multiplexed and scalable system will dramatically lower the cost-per-target in primary and secondary drug screens, thereby relieving a major bottleneck in the development of therapeutic interventions for numerous diseases and conditions. Further, because the system will employ automated instrumentation that is already in place in numerous industrial and academic laboratories, barriers to adoption will be very low.
Public Health Relevance Statement: Project Narrative. Our goal is to develop an automated system that detects and quantifies the responses of numerous GPCRs in parallel by interrogating microarrays of reverse-transfected mammalian cells. The system will improve drug discovery by enabling chemical and biologic libraries to be screened against many targets in parallel, and it will improve drug development by revealing the basis of unintended side effects that can be addressed to produce more precisely targeted, and more effective, therapeutic molecules.
Project Terms: abstracting; Address; Adoption; Adrenergic Receptor; Adverse effects; Agonist; base; Basic Science; Benchmarking; Biological Assay; Cells; Chemicals; chemokine receptor; cost; Data; Detection; Development; Disease; DNA Microarray Chip; Dose; drug development; drug discovery; Flow Cytometry; Fluorescence Microscopy; G-Protein-Coupled Receptors; Gene Chips; Genetic Vectors; Goals; Human; improved; instrumentation; Kinetics; Laboratories; Libraries; Life; Mammalian Cell; Methods; miniaturize; next generation sequencing; Optics; Pattern; Pharmaceutical Preparations; Preclinical Drug Evaluation; Printing; Proteins; receptor; receptor downregulation; response; screening; System; targeted treatment; Technology; Therapeutic; Therapeutic Intervention; TimeLine; tool; Transcript; Transfection; vector
