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，大约有4,000个被 制药公司。然而，只有不到10%的这些可药物蛋白质实际上是FDA批准的靶标 毒品。2014年，美国国立卫生研究院启动了照明可药物基因组(IDG)项目，以表彰 有大量潜在的具有高治疗价值的可用药靶点尚未发现 或未被充分研究。IDG选择了230个G蛋白偶联受体(GPCRs)和离子通道作为重点 他们的计划，因为这些家族构成了可药物基因组中最大的家族，具有很高的潜力 影响人类健康。由于生物学上的困难，它们中的许多都完全没有被探索过。要启用此功能，请执行以下操作 研究表明，IDG呼吁开发抗病毒的单抗等试剂。 这230个GPCR和离子通道，其中目前只有10%拥有商业上可用的MAb。一本小说 需要一种高通量鉴定膜蛋白单抗的方法来获得针对 整个可下药的人类细胞膜蛋白质组。

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.