Change search
ReferencesLink to record
Permanent link

Direct link
An engineered affibody molecule with pH-dependent binding to FcRn mediates extended circulatory half-life of a fusion protein
KTH, School of Biotechnology (BIO), Protein Technology.
Show others and affiliations
2014 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 48, 17110-17115 p.Article in journal (Refereed) Published
Abstract [en]

Proteins endocytosed from serum are degraded in the lysosomes. However, serum albumin (SA) and IgG, through its Fc part, bind to the neonatal Fc receptor (FcRn) at low pH in the endosome after endocytosis, and are transported back to the cellular surface, where they are released into the bloodstream, resulting in an extended serum circulation time. Association with Fc or SA has been used to prolong the in vivo half-life of biopharmaceuticals, using the interaction with FcRn to improve treatment regimens. This has been achieved either directly, by fusion or conjugation to Fc or SA, or indirectly, using SA-binding proteins. The present work takes this principle one step further, presenting small affinity proteins that bind directly to FcRn, mediating extension of the serum half-life of fused biomolecules. Phage display technology was used to select affibody molecules that can bind to FcRn in the pH-dependent manner required for rescue by FcRn. The biophysical and binding properties were characterized in vitro, and the affibody molecules were found to bind to FcRn more strongly at low pH than at neutral pH. Attachment of the affibody molecules to a recombinant protein, already engineered for increased halflife, resulted in a nearly threefold longer half-life in mice. These tags should have general use as fusion partners to biopharmaceuticals to extend their half-lives in vivo.

Place, publisher, year, edition, pages
2014. Vol. 111, no 48, 17110-17115 p.
Keyword [en]
affibody molecule, neonatal Fc receptor, ABD, albumin-binding domain, pharmacokinetics
National Category
Other Biological Topics
URN: urn:nbn:se:kth:diva-158270DOI: 10.1073/pnas.1417717111ISI: 000345920800040PubMedID: 25406323ScopusID: 2-s2.0-84915818878OAI: diva2:778122
Knut and Alice Wallenberg Foundation

QC 20150109

Available from: 2015-01-09 Created: 2015-01-07 Last updated: 2015-01-09Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Seijsing, JohanLöfblom, JohnUhlén, MathiasGräslund, Torbjörn
By organisation
Protein TechnologyProteomics and Nanobiotechnology
In the same journal
Proceedings of the National Academy of Sciences of the United States of America
Other Biological Topics

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 58 hits
ReferencesLink to record
Permanent link

Direct link