The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Extending Serum Half-life of Albumin by Engineering Neonatal Fc Receptor (FcRn) Binding
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“This occurs at a lower rate in health.22”
From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [22]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Crystal structure of human serum albumin at 2.5 Å resolution
Sugio, S., Kashima, A., Mochizuki, S., Noda, M., & Kobayashi, K. (1999) · Protein Engineering Design and Selection · doi:10.1093/protein/12.6.439 · Cited by 1,816
Curry, S., Mandelkow, H., Brick, P., & Franks, N. P. (1998) · Nature Structural Biology · doi:10.1038/1869 · Cited by 1,378
Quantitative analysis of protein far UV circular dichroism spectra by neural networks
Böhm, G., Muhr, R., & Jaenicke, R. (1992) · Protein Engineering Design and Selection · doi:10.1093/protein/5.3.191 · Cited by 1,114
Impact of albumin on drug delivery — New applications on the horizon
Elsadek, B., & Kratz, F. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.09.069 · Cited by 853
Therapeutic antibodies for autoimmunity and inflammation
Chan, A. C., & Carter, P. J. (2010) · Nature reviews. Immunology · doi:10.1038/nri2761 · Cited by 846
Enhanced antibody half-life improves in vivo activity
Zalevsky, J., Chamberlain, A. K., Horton, H. M., Karki, S., Leung, I., Sproule, T. J., Lazar, G. A., Roopenian, D. C., & Desjarlais, J. R. (2010) · Nature Biotechnology · doi:10.1038/nbt.1601 · Cited by 667
Chaudhury, C., Mehnaz, S., Robinson, J. M., Hayton, W. L., Pearl, D. K., Roopenian, D. C., & Anderson, C. L. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021829 · Cited by 640
Albumin as a versatile platform for drug half-life extension
Sleep, D., Cameron, J., & Evans, L. R. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.04.023 · Cited by 510
Self-citationCrystal structural analysis of human serum albumin complexed with hemin and fatty acid
Zunszain, P. A., Ghuman, J., Komatsu, T., Tsuchida, E., & Curry, S. (2003) · BMC Structural Biology · doi:10.1186/1472-6807-3-6 · Cited by 509
Ober, R. J., Radu, C. G., Ghetie, V. F., & Ward, E. S. (2001) · International Immunology · doi:10.1093/intimm/13.12.1551 · Cited by 502
Crystal structure of the complex of rat neonatal Fc receptor with Fc
Burmeister, W. P., Huber, A. H., & Björkman, P. J. (1994) · Nature · doi:10.1038/372379a0 · Cited by 442
Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels
Vaccaro, C., Zhou, J., Ober, R. J., & Ward, E. S. (2005) · Nature Biotechnology · doi:10.1038/nbt1143 · Cited by 407
Crystal structure of the complex of rat neonatal Fc receptor with Fc
(1995) · Trends in Genetics · doi:10.1016/0168-9525(95)90005-5 · Cited by 382
Story, C. M., Mikulska, J., & Simister, N. E. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.6.2377 · Cited by 354
Petkova, S. B., Akilesh, S., Sproule, T. J., Christianson, G. J., Khabbaz, H. J. A., Brown, A. C., Presta, L. G., Meng, Y. G., & Roopenian, D. C. (2006) · International Immunology · doi:10.1093/intimm/dxl110 · Cited by 319
Albumin Binding to FcRn: Distinct from the FcRn−IgG Interaction
Chaudhury, C., Brooks, C. L., Carter, D. C., Robinson, J. M., & Anderson, C. L. (2006) · Biochemistry · doi:10.1021/bi052628y · Cited by 290
Engineered Human IgG Antibodies with Longer Serum Half-lives in Primates
Hinton, P. R., Johlfs, M. G., Xiong, J. M., Hanestad, K., Ong, K. C., Bullock, C., Keller, S., Tang, M. T., Tso, J. Y., Vásquez, M., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c300470200 · Cited by 277
Neonatal FcR Expression in Bone Marrow-Derived Cells Functions to Protect Serum IgG from Catabolism
Akilesh, S., Christianson, G. J., Roopenian, D. C., & Shaw, A. S. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.7.4580 · Cited by 276
Crystallographic Analysis of Human Serum Albumin Complexed with 4Z,15E-Bilirubin-IXα
Zunszain, P. A., Ghuman, J., McDonagh, A. F., & Curry, S. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.06.016 · Cited by 267
West, A. P., & Björkman, P. J. (2000) · Biochemistry · doi:10.1021/bi000749m · Cited by 261
Structural Insights into Neonatal Fc Receptor-based Recycling Mechanisms
Oganesyan, V., Damschroder, M. M., Cook, K. E., Li, Q., Gao, C., Wu, H., & Dall'Acqua, W. F. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.537563 · Cited by 259
Increasing the serum persistence of an IgG fragment by random mutagenesis
Ghetie, V. F., Popov, S. G., Borvak, J., Radu, C. G., Matesoi, D., Medesan, C., Ober, R. J., & Ward, E. S. (1997) · Nature Biotechnology · doi:10.1038/nbt0797-637 · Cited by 253
Montoyo, H. P., Vaccaro, C., Hafner, M., Ober, R. J., Mueller, W., & Ward, E. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810796106 · Cited by 211
Structure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor
Andersen, J. T., Dalhus, B., Cameron, J., Daba, M. B., Plumridge, A., Evans, L. R., Brennan, S. O., Gunnarsen, K. S., Bjørås, M., Sleep, D., et al. (2012) · Nature Communications · doi:10.1038/ncomms1607 · Cited by 206
Self-citationAndersen, J. T., Daba, M. B., Berntzen, G., Michaelsen, T. E., & Sandlie, I. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.081828 · Cited by 200
Self-citationSantagostino, E., Négrier, C., Klamroth, R., Tiede, A., Pabinger-Fasching, I., Voigt, C., Jacobs, I. C., & Morfini, M. (2012) · Blood · doi:10.1182/blood-2012-05-429688 · Cited by 177
Andersen, J. T., & Sandlie, I. (2009) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.24.318 · Cited by 124
Self-citationAndersen, J. T., Qian, J. D., & Sandlie, I. (2006) · European Journal of Immunology · doi:10.1002/eji.200636556 · Cited by 123
Self-citationSchmidt, M. M., Townson, S. A., Andreucci, A., King, B. M., Schirmer, E. B., Murillo, A., Dombrowski, C., Tisdale, A. W., Lowden, P., Masci, A., et al. (2013) · Structure · doi:10.1016/j.str.2013.08.022 · Cited by 121
An FcRn-Dependent Role for Anti-flagellin Immunoglobulin G in Pathogenesis of Colitis in Mice
Kobayashi, K., Qiao, S., Yoshida, M., Baker, K., Lencer, W. I., & Blumberg, R. S. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.07.059 · Cited by 88
Andersen, J. T., Cameron, J., Plumridge, A., Evans, L. R., Sleep, D., & Sandlie, I. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.463000 · Cited by 68
Self-citationSimister, N. E., & Mostov, K. E. (1989) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1989.054.01.068 · Cited by 64
Evans, L. R., Hughes, M., Waters, J., Cameron, J., Dodsworth, N., Tooth, D., Greenfield, A., & Sleep, D. (2010) · Protein Expression and Purification · doi:10.1016/j.pep.2010.05.009 · Cited by 40
Self-citationFcRn binding properties of an abnormal truncated analbuminemic albumin variant
Andersen, J. T., Daba, M. B., & Sandlie, I. (2009) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2009.12.001 · Cited by 35
Self-citationAndersen, J. T., Justesen, S. F. L., Fleckenstein, B. T., Michaelsen, T. E., Berntzen, G., Kenanova, V. E., Daba, M. B., Lauvrak, V., Buus, S., & Sandlie, I. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06551.x · Cited by 31
Self-citationA homozygote for a serum albumin variant of the fast type
Vanzetti, G., Porta, F., Prencipe, L., Scherini, A., & Fraccaro, M. (1979) · Human Genetics · doi:10.1007/bf00278896 · Cited by 11
Cited by
Sorted by citations
Hypoalbuminemia: Pathogenesis and Clinical Significance
Soeters, P. B., Wolfe, R. R., & Shenkin, A. (2019) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.1451 · Cited by 1,448
Albumin-based drug delivery: harnessing nature to cure disease
Larsen, M. T., Kuhlmann, M., Hvam, M. L., & Howard, K. A. (2016) · Molecular and Cellular Therapies · doi:10.1186/s40591-016-0048-8 · Cited by 704
Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters
Strohl, W. R. (2015) · BioDrugs · doi:10.1007/s40259-015-0133-6 · Cited by 479
Albumin and its application in drug delivery
Sleep, D. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2015.993313 · Cited by 470
Self-citationThe Neonatal Fc Receptor (FcRn): A Misnomer?
Pyzik, M., Sand, K. M. K., Hubbard, J. J., Andersen, J. T., Sandlie, I., & Blumberg, R. S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01540 · Cited by 450
Self-citation
Metadata
- 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
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 289
- Issue
- 19
- Pages
- 13492-13502
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4036356
- 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
- hybrid
- doi.org
- Licence
- 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
- Life Sciences › Immunology and Microbiology › Immunology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review