Extending Serum Half-life of Albumin by Engineering FcRn Binding
نویسندگان
چکیده
1 Centre for Immune Regulation (CIR) and Department of Biosciences, University of Oslo, N-0316 Oslo, Norway. 2 CIR and Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Norway, PO Box 4950, N-0424 Oslo, Norway. 3 Department for Microbiology, Oslo University Hospital Rikshospitalet and University of Oslo, PO Box 4950, Nydalen, N-0424 Oslo, Norway. 4 Department of Medical Biochemistry, Oslo University Hospital Rikshospitalet and University of Oslo, PO Box 4950, Nydalen, N-0424 Oslo, Norway. 5 Novozymes Biopharma UK Ltd., Castle Court, 59 Castle Boulevard, NG7 1FD Nottingham, United Kingdom. 6 Novozymes A/S, Krogshoejvej 36, 2880 Bagsvaerd, Denmark.
منابع مشابه
Extending half-life by indirect targeting of the neonatal Fc receptor (FcRn) using a minimal albumin binding domain.
The therapeutic and diagnostic efficiency of engineered small proteins, peptides, and chemical drug candidates is hampered by short in vivo serum half-life. Thus, strategies to tailor their biodistribution and serum persistence are highly needed. An attractive approach is to take advantage of the exceptionally long circulation half-life of serum albumin or IgG, which is attributed to a pH-depen...
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We generated an anti-albumin antibody, CA645, to link its Fv domain to an antigen-binding fragment (Fab), thereby extending the serum half-life of the Fab. CA645 was demonstrated to bind human, cynomolgus, and mouse serum albumin with similar affinity (1-7 nM), and to bind human serum albumin (HSA) when it is in complex with common known ligands. Importantly for half-life extension, CA645 binds...
متن کاملDissection of the neonatal Fc receptor (FcRn)-albumin interface using mutagenesis and anti-FcRn albumin-blocking antibodies.
Albumin is the most abundant protein in blood and plays a pivotal role as a multitransporter of a wide range of molecules such as fatty acids, metabolites, hormones, and toxins. In addition, it binds a variety of drugs. Its role as distributor is supported by its extraordinary serum half-life of 3 weeks. This is related to its size and binding to the cellular receptor FcRn, which rescues albumi...
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Albumin is the most abundant protein in blood where it has a pivotal role as a transporter of fatty acids and drugs. Like IgG, albumin has long serum half-life, protected from degradation by pH-dependent recycling mediated by interaction with the neonatal Fc receptor, FcRn. Although the FcRn interaction with IgG is well characterized at the atomic level, its interaction with albumin is not. Her...
متن کاملThe versatile MHC class I-related FcRn protects IgG and albumin from degradation: implications for development of new diagnostics and therapeutics.
SUMMARY The half-life of the two most abundant proteins in blood, immunoglobulin G (IgG) and serum albumin, is extraordinary (approximately 19-23 days) compared to other circulating proteins. This phenomenon secures a broad biodistribution throughout the body of both molecules. The long half-life has made IgG the natural choice for engineering of antibody based therapeutics, while albumin is us...
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