Cited by 167Monoclonal and Polyclonal Antibodies ResearchProtein Interaction Studies and Fluorescence AnalysisProtein purification and stability

Extending Serum Half-life of Albumin by Engineering Neonatal Fc Receptor (FcRn) Binding

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Andersen, Jan Terje, Dalhus, Bjørn, Viuff, Dorthe, Ravn, Birgitte Thue, Gunnarsen, Kristin Støen, Plumridge, Andrew, Bunting, Karen, Antunes, Filipa +9 more·2014·Journal of Biological Chemistry

Abstract

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.

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Crossref · 10.1074/jbc.m114.549832

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  • This process occurs at a lower rate in health.

    “This occurs at a lower rate in health.22”

    From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [22]

    The paper describes FcRn-mediated albumin recycling (Introduction, p. 1) and compares the half-lives of engineered and wild-type albumin (p. 5). It does not identify what “this” refers to or compare its rate in health with its rate in disease; searches for a health–disease rate comparison found no such passage. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Authors
Andersen, J. T., Dalhus, B., Viuff, D., Ravn, B. T., Gunnarsen, K. S., Plumridge, A., Bunting, K., Antunes, F., Williamson, R., Athwal, S., Allan, E., Evans, L., Bjørås, M., Kjærulff, S., Sleep, D., Sandlie, I., & Cameron, J.
Affiliations
  • University of Oslo (NO)
  • Oslo University Hospital (NO)
  • Novozymes (United Kingdom) (GB)
  • Novozymes (Denmark) (DK)
Corresponding author
  • Andersen, Jan Terje
  • Cameron, Jason
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2014-05
Volume
289
Issue
19
Pages
13492-13502
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2088696708
Cited by
167
References
37
Citations by year
2026: 12 · 2025: 13 · 2024: 11 · 2023: 14 · 2022: 12 · 2021: 22 · 2020: 15 · 2019: 11 · 2018: 16 · 2017: 9 · 2016: 14 · 2015: 13 · 2014: 5
FWCI
10.69
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
Keywords
human serum albumin, neonatal Fc receptor, serum half-life, albumin variants, scFv, Macaca fascicularis, biopharmaceuticals
MeSH terms
Albumins, Animals, Female, Half-Life, Humans, Macaca fascicularis, Receptors, Fc, Recombinant Fusion Proteins, Histocompatibility Antigens Class I, Amino Acid Substitution, Mutation, Missense, Mice

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