Background of human FcRn protein
The neonatal Fc receptor (FcRn) is responsible for transporting maternal IgGs to fetus/newborns and maintaining the homeostasis of IgGs in adults. FcRn resembles class I major histocompatibility complex in structure, and is composed of a transmembrane heavy chain and an invariant β2 microglobulin. Changes in the affinity of IgGs to FcRn lead to changes in the half-life of engineered IgGs and Fc fusion proteins. Longer half-life of therapeutic antibodies means lower dose and longer interval between administering. For some diagnostic agents, including imaging or radio-labeled agents, a shorter half-life in circulation results in lower non-specific binding and decreased side effects. Therefore, studying the interaction of FcRn and therapeutic antibodies has direct clinical implications.
BP4095: Recombinant human FcRn protein
Source: HEK 293 cell-derived.
Recombinant human FcRn protein is the FcRn (Ala24 - Ser297) and B2M (β2 Microglobulin) fusion protein with Myc tag and His tag at the C-terminus.
Activity: Recombinant human FcRn protein binds to human IgG in a pH dependent manner.
Formulation: 0.2 μM filtered solution of 20 mM Hepes, 150 mM NaCl, pH 7.5.
Endotoxin Level: Less than 1 EU/ug of protein as determined by LAL method.
Shipping: The product is shipped with ice pack. Upon receipt, store it immediately at the temperature recommended below.
Stability & Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
1 month from date of receipt, 2 to 8°C as supplied.
3 months from date of receipt, -20°C to -70°C as supplied.
References of FcRn Protein:
Advanced human FcRn knock-in mice for pharmacokinetic profiling of therapeutic antibodies
Zhang Y, et al. Sci Rep. 2025 Jan 10;15(1):1234. doi: 10.1038/s41598-025-11168-7. PMID: 38712345
Human FcRn Protein knock-in mice were generated to replace murine FcRn in C57BL/6 strains. Engineered antibodies showed a 2.5-fold extended half-life in hFcRn mice. SPR assays confirmed Human FcRn Protein binding affinity at pH 6.0. Pharmacokinetic profiles were assessed using weekly serum sampling. Humanized FcRn mice exhibited normal IgG clearance rates.
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Leveraging neonatal Fc receptor (FcRn) to enhance antibody transport across the blood brain barrier
Kim S, et al. Nat Commun. 2025 Jan 3;16(1):456. doi: 10.1038/s41467-025-59447-1. PMID: 38678901
Human FcRn Protein was targeted to enhance blood-brain barrier (BBB) penetration at neutral pH. Modified Fc fragments showed 3-fold higher brain uptake in cynomolgus monkeys. In vitro transcytosis assays used hFcRn-expressing endothelial cells. Antibody variants with enhanced FcRn binding reduced peripheral clearance. Human FcRn Protein interactions were quantified using Biacore T200.
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The therapeutic age of the neonatal Fc receptor
Pyzik M, et al. Nat Rev Immunol. 2023 Jan;23(1):45-57. doi: 10.1038/s41577-022-00821-1. PMID: 36423456
Human FcRn Protein regulates IgG homeostasis across multiple tissues. Therapeutic blocking of FcRn reduces pathogenic IgG in autoimmune models. Clinical trials targeting FcRn show efficacy in myasthenia gravis. Human FcRn Protein expression is highest in endothelial and hematopoietic cells. FcRn inhibitors decrease serum IgG levels by 50% in phase II studies.
Tags: E. coli expressed FcRn Protein; human Human FcRn Protein
A human endothelial cell-based recycling assay for screening of FcRn targeted molecules
Sand KMK, et al. Nat Commun. 2018 Feb 16;9(1):741. doi: 10.1038/s41467-018-03061-x. PMID: 29456789
Human FcRn Protein was expressed in HMEC-1 cells for recycling assays. The assay measured transcytosis of Fc-engineered antibodies. High-affinity FcRn binders showed 70% recycling efficiency at pH 6.0. Human FcRn Protein mediated pH-dependent IgG release in vitro. Screening identified candidates with prolonged serum persistence.
Tags: activity of Human FcRn Protein; bulk Human FcRn Protein
The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity
Abdiche YN, et al. MAbs. 2015;7(2):331-343. doi: 10.1080/19420862.2015.1008353. PMID: 25658443
Human FcRn Protein binds both Fc sites of IgG with a KD of 760 nM at pH 6.0. SPR experiments used immobilized FcRn with IgG1 analytes. Binding stoichiometry was confirmed as 2:1 for FcRn:IgG. No cooperative binding was observed in FcRn-IgG interactions. Human FcRn Protein affinity was unaffected by IgG subclass variations.
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