The neonatal Fc receptor (FcRn): a homeostatic regulator of IgG and albumin

The serum half-life of the two most abundant proteins in blood, IgG and albumin, is three weeks in humans, while other circulating proteins are removed from the body within minutes, hours or a few days. The long half-life has made IgG the preferred choice when engineering antibody-based therapeutics, while albumin is increasingly used as a carrier of drugs. Remarkably, basic research has unraveled that the long half-life of these completely unrelated proteins is achieved through a common mechanism, as both are rescued from degradation inside cells that line the blood vessels after binding to a receptor named the neonatal Fc receptor (FcRn). Hence, increasing appreciation for the unique role of FcRn has triggered intense interest from both academia and biotech companies, as such knowledge has tremendous implications for our understanding of the biology of IgG and albumin, and not at least how they can be utilized in development of novel drugs. This is of great importance as many promising peptide and protein based drugs have very short half-lives and thus do not work properly.

To tailor the next generation of IgG and albumin based therapeutics, a complete understanding on how FcRn binds its ligands and how it acts as a transporter in different cell types of the body is needed. Thus, our laboratory aims to unravel the basic structural and cellular mechanisms that govern the function of FcRn, with a particular focus on albumin as a multifunctional transporter of essential molecules. Such knowledge offers opportunities for development of therapeutic concepts that will secure improved half-life and biodistribution that will be efficient and cost effective.