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Updated: Jan 16, 2026

High-resolution Confocal Imaging of the Blood-brain Barrier: Imaging, 3D Reconstruction, and Quantification of Transcytosis
Published on: November 16, 2017
Antibody Engineering for Receptor-Mediated Transcytosis Across the Blood-Brain Barrier
Kaiyuan Guo1, Dinglingge Cao1, Lucia P Marchese-Thomas1
1Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Abstract:
Efficient delivery of therapeutic antibodies into the central nervous system (CNS) remains severely limited by the restrictive nature of the blood-brain barrier (BBB). Receptor-mediated transcytosis (RMT) has emerged as a promising strategy to enhance antibody transport across the BBB. In this Viewpoint, we highlight recent advances in RMT-based antibody delivery, focusing specifically on three representative BBB receptors: transferrin receptor (TfR), insulin receptor (InsR), and neonatal Fc receptor (FcRn). By comparing antibody engineering strategies that target these receptors, we summarize current progress, discuss critical limitations, and suggest directions for advancing CNS-targeted therapeutic antibodies. This Viewpoint provides valuable insights for selecting appropriate RMT targets and optimizing antibody-based therapies for CNS diseases.

