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J Biol Chem. 2014 May 9;289(19):13492-502. doi: 10.1074/jbc.M114.549832. Epub 2014 Mar 20.

Extending serum half-life of albumin by engineering neonatal Fc receptor (FcRn) binding.

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From the Centre for Immune Regulation and Department of Biosciences, University of Oslo, N-0316 Oslo, Norway.


A major challenge for the therapeutic use of many peptides and proteins is their short circulatory half-life. Albumin has an extended serum half-life of 3 weeks because of its size and FcRn-mediated recycling that prevents intracellular degradation, properties shared with IgG antibodies. Engineering the strictly pH-dependent IgG-FcRn interaction is known to extend IgG half-life. However, this principle has not been extensively explored for albumin. We have engineered human albumin by introducing single point mutations in the C-terminal end that generated a panel of variants with greatly improved affinities for FcRn. One variant (K573P) with 12-fold improved affinity showed extended serum half-life in normal mice, mice transgenic for human FcRn, and cynomolgus monkeys. Importantly, favorable binding to FcRn was maintained when a single-chain fragment variable antibody was genetically fused to either the N- or the C-terminal end. The engineered albumin variants may be attractive for improving the serum half-life of biopharmaceuticals.


Albumin; Animal Models; Antibody Engineering; Biodegradation; Bioengineering; FC Receptors; Pharmacokinetics; pH Regulation

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