High-throughput Discovery of Antibodies against Understudied Membrane Proteins

ABSTRACT Of the 20,000 genes in the human genome, approximately 4,000 are considered “druggable” by pharmaceuticals. However, less than 10% of these druggable proteins are actually targeted by FDA-approved drugs. In 2014, the Illuminating the Druggable Genome (IDG) project was launched by the NIH in recognition that there is a potentially large number of druggable targets with high therapeutic value that are undiscovered or understudied. The IDG selected 230 G protein-coupled receptors (GPCRs) and ion channels as a focus of their program, as these families make up the largest families of the druggable genome and have high potential to impact human health. Due to their difficult biology, many of them are completely unexplored. To enable this research, the IDG has called for the development of reagents such as monoclonal antibodies (MAbs) against these 230 GPCRs and ion channels, only 10% of which currently have commercially available MAbs. A novel approach to identify membrane protein MAbs in a high-throughput manner is needed to derive MAbs against the entire druggable human membrane proteome.