Double-Humanized Serum Albumin/Neonatal Fc Receptor Mouse Model
Our double-humanized serum albumin/neonatal Fc receptor mouse model (HSA/hFcRn) maintains an autologous receptor-ligand interaction and can mimic the physiological drug clearance in humans.
Applications
- Accurate and predictive PK/PD studies of albumin- and FcRn-binding compounds
- Development of conventional drugs and biologics with enhanced half-life through interaction with HSA and hFcRn
- Assessment of a variety of compounds, including albumin variants, small molecules, antibody-like biologics and antibodies, including T-cell engagers
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HSA/hFcRn model features
- Physiological HSA and hFcRn expression profile and regulation in a mouse system, as they are both controlled by their respective endogenous mouse promoters
- Physiological expression level of human albumin in a mouse system (within the normal range of 1.5-6 g/dL)
- Normal blood chemistry compared to a wild-type mouse
- Murine SA and FcRn expression is abolished
HSA/hFcRn model validation
The model has been co-validated by Albumedix, the biopharmaceutical operations spin out of Novozymes.
Expression of hFcRn is physiological in HSA/hFcRn mice A. hFcRn expression was determined by qPCR in duodenum (Du), jejunum (Je), ileum (iLe), large intestine (Li), liver (H), kidney (K), and lung (Lu). B-D. hFcRn immunohistochemical staining of sections from humanized (large image) and wild-type (small insert) mice duodenum (B), jejunum (C), and ileum (D). No cross reactivity to mouse FcRn was seen in wild-type mice (small insert). |
Half-life of drugs conjugated to human albumin is significantly extended in HSA/hFcRn mice
Albumin-bound drug 1: low affinity for hFcRn |
* For more validation data please contact us.
The double-humanized HSA/hFcRn mouse can be intercrossed with any model of interest, including our humanized immune checkpoint mice.
Reference
Elisabeth Fuchs, Imke Rudnik-Jansen, Anders Dinesen, Denis Selnihhin, Ole Aalund Mandrup, Kader Thiam, Jørgen Kjems, Finn Skou Pedersen, Kenneth A Howard.
An albumin-angiotensin converting enzyme 2-based SARS-CoV-2 decoy with FcRn-driven half-life extension.
Acta Biomater. 2022 Nov
Dasom Kim, Jin-Ho Park, Tae-Yoon Kim, Dong-Gun Kim, June-Ho Byun, Hak-Sung Kim.
Enhanced half-life and antitumor activity of interleukin-15 through genetic fusion of a serum albumin-specific protein binder.
Int J Pharm. 2022 Sep 25
Marta Duran-Güell, Roger Flores-Costa, Mireia Casulleras, Cristina López-Vicario, Esther Titos, Alba Díaz, José Alcaraz-Quiles, Raquel Horrillo, Montserrat Costa, Javier Fernández, Vicente Arroyo, Joan Clària.
Albumin protects the liver from tumor necrosis factor α-induced immunopathology.
FASEB J. 2021 Feb
Viuff D, Antunes F, Evans L, Cameron J, Dyrnesli H, Thue Ravn B, Stougaard M, Thiam K, Andersen B, Kjærulff S, Howard KA.
Generation of a double transgenic humanized neonatal Fc receptor (FcRn)/albumin mouse to study the pharmacokinetics of albumin-linked drugs.
J Control Release. 2016 Feb 10.
Further reading
- Immunocompromised HSA/hFcRn Mouse Model: A New Xenograft Model for Efficacy Studies of Immunotherapies
- HSA/hFcRn, a Powerful Model for Your PK/PD Studies
Ready to be shipped to your lab
- Cohorts available upon request
- Studies can be carried out at your site or at your favorite CRO
- SOPF certification and worldwide delivery by professional breeders
- Models provided with FTO on patent-protected technologies used for model generation