A humanized transferrin receptor 1-transferrin model supports functional iron homeostasis and therapeutic delivery across the blood-brain barrier.

ABSTRACT: The transferrin receptor 1 (TfR1)-transferrin (TF) axis is central to iron homeostasis and represents a validated route for delivering biologics across the blood-brain barrier (BBB). We developed human-specific anti-TfR1 nanobodies (NewroBus) that exploit this pathway, but their lack of cross-reactivity with rodent TfR1 limits conventional preclinical testing. To overcome this, we generated knock-in rats in which the coding sequences of the endogenous Tfrc and Tf genes were replaced with their human counterparts, producing animals that express human TfR1 and/or human TF under physiological control. Rats homozygous for both humanized alleles were viable and fertile, indicating functional replacement of their rodent orthologs but exhibited erythropoietic abnormalities and altered iron distri

SUBMITTER: Yesiltepe M 

PROVIDER: S-EPMC12799929 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature