The NewroBus platform: engineered humanized anti-TfR1 nanobodies for efficient brain delivery.

ABSTRACT:

Background

Delivery of biologic therapeutics to the central nervous system (CNS) is hindered by the blood-brain barrier (BBB), which restricts large molecule passage. Receptor-mediated transcytosis via transferrin receptor 1 (TfR1) provides a physiological route for selective BBB transport. This study aimed to develop human-specific nanobodies that engage TfR1 without disrupting transferrin function, enabling safe and efficient CNS delivery of therapeutic biologics.

Methods

Single-domain camelid antibodies targeting human TfR1 were isolated, humanized, and optimized through computational and artificial intelligence-guided algorithms to improve humanness, solubility, and stability. Binding kinetics were quantified by surface plasmon resonance using a 1:1 Langmuir model. In vi

SUBMITTER: Yin T 

PROVIDER: S-EPMC12853688 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature