Design antibodies that effectively reach the CNS

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Overcome the challenge of BBB crossing

Developing therapeutic antibodies for CNS conditions remains highly challenging. Despite advances in transferrin receptor (TFRC or CD71)-mediated delivery, evaluating antibody transport across the blood-brain barrier (BBB) is still limited by poor translatability of standard preclinical models, leading to uncertainty in CNS exposure and efficacy.

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A translational solution: the genO-hTFRC model

genO-hTFRC mice enable reliable in vivo efficacy assessment of CNS-targeting antibodies, by providing physiological expression of humanized TFRC in relevant tissues, such as bone marrow and blood. This allows you to better evaluate BBB crossing strategies and confidently advance your therapeutic candidates.

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Why the genO‑hTFRC model makes the difference

Physiological expression for predictive data

genO‑hTFRC mice express human TFRC in the brain and liver (Figure 1A), while preserving normal iron regulation and transferrin internalisation (Figure 1B) comparable to wild‑type mice.

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**Figure 1 –** Physiological expression and functionality of hTFRC. A) The genO-hTFRC model expresses hTFRC in the brain and liver in similar levels of those observed in WT mice (C57BL/6J). B) Transferrin endocytosis is preserved in genO-hTFRC mice, implying that hTFRC is functional.

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**Proven in vivo efficacy assessment**

The model enables robust profiling of antibodies targeting human TFRC and designed for BBB transport (Figure 2), supporting translational evaluation of CNS delivery strategies, which was validated by Lundbeck, and presented at the AACR 2024:

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**Figure 2 -** Efficacy assessment of anti-BACE1 antibody. Treatment with Lundbeck’s anti-TFRC/anti-BACE1 antibody leads to decreased levels of Amyloid β in the brain.

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Advanced evaluation of antibody engineering

Combined with genO-hFcγR and genO-hSA/hFcRn intercrosses, these models allow reliable evaluation of Fc-engineering strategies, helping you balance BBB transport, efficacy and antibody half-life with greater translational confidence:

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