High-throughput Discovery of Antibodies against Understudied Membrane Proteins

摘要 在人类基因组中的20，000个基因中，大约4，000个被认为是“可药物化的”。 大药厂然而，这些可药用蛋白质中只有不到10%实际上是FDA批准的靶向蛋白质。 毒品2014年，美国国立卫生研究院（NIH）启动了照亮可药用基因组（IDG）项目， 有大量潜在的具有高治疗价值的药物靶点尚未发现， 或者是替补演员IDG选择了230个G蛋白偶联受体（GPCR）和离子通道作为研究的重点。 他们的计划，因为这些家庭组成了最大的家庭的药物基因组，并具有很高的潜力， 影响人类健康。由于其复杂的生物学，其中许多是完全未开发的。要启用此 研究，IDG呼吁开发试剂，如单克隆抗体（MAbs）， 这些230个GPCR和离子通道，其中只有10%目前有商业上可获得的单克隆抗体。一种新型 需要一种以高通量方式鉴定膜蛋白单克隆抗体的方法来获得抗 整个可药用的人类膜蛋白质组

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.