Double-humanized HSA/hFcRn mouse model
Use this double humanized HSA/hFcRn mouse model for accurate and predictive PK/PD studies of albumin- and FcRn-binding compounds.
Applications
- Accurate and predictive PK/PD studies of albumin- and FcRn-binding compounds
- Development of conventional drugs and biologics with enhanced half-lifethrough interaction with HSA and hFcRn
- Assessment of a variety of compounds, including albumin variants, small molecules, antibody-like biologics and antibodies, including T-cell engager
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
Validation
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
Albumin-bound drug 2: high affinity for hFcRn
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HSA/hFcRn
Double-humanized HSA/hFcRn mouse model
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