The blood-brain barrier (BBB) serves as a crucial defense for the brain but presents a major obstacle for CNS drug development. Less than 5% of drugs successfully cross the BBB, making research in this area costly and time-consuming. To advance the field, innovative solutions are needed to improve drug delivery to the brain.

By replacing key mouse targets involved in natural BBB transport—like TFR1 and CD98HC—with their human counterparts, we enable more precise in vivo testing of CNS drug delivery mechanisms using humanized candidates. A study published in Science using our B-hTFR1 mice demonstrated that an optimized AAV, designed to bind human TFR1, successfully penetrated the CNS and delivered a therapeutically relevant protein missing in Gaucher disease.