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An engineered affib...
An engineered affibody molecule with pH-dependent binding to FcRn mediates extended circulatory half-life of a fusion protein
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- Seijsing, Johan (författare)
- KTH,Proteinteknologi
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Lindborg, Malin (författare)
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Höidén-Guthenberg, Ingmarie (författare)
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visa fler...
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Bönisch, Heiko (författare)
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Guneriusson, Elin (författare)
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- Frejd, Fredrik Y. (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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Abrahmsén, Lars (författare)
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Ekblad, Caroline (författare)
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- Löfblom, John (författare)
- KTH,Proteinteknologi
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- Uhlén, Mathias (författare)
- KTH,Proteomik och nanobioteknologi
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- Gräslund, Torbjörn (författare)
- KTH,Proteinteknologi
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(creator_code:org_t)
- 2014-11-18
- 2014
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:48, s. 17110-17115
- Relaterad länk:
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https://www.pnas.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Annan biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Other Biological Topics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
Nyckelord
- affibody molecule
- neonatal Fc receptor
- ABD
- albumin-binding domain
- pharmacokinetics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Seijsing, Johan
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Lindborg, Malin
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Höidén-Guthenber ...
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Bönisch, Heiko
-
Guneriusson, Eli ...
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Frejd, Fredrik Y ...
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visa fler...
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Abrahmsén, Lars
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Ekblad, Caroline
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Löfblom, John
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Uhlén, Mathias
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Gräslund, Torbjö ...
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Annan biologi
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- MEDICIN OCH HÄLSOVETENSKAP
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Kungliga Tekniska Högskolan
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Uppsala universitet