Brain shuttle peptides derived from phage display.

Vascular beds within different tissues, including the brain, exhibit diverse molecular heterogeneity. Screening of peptide libraries using in vivo phage display exploits this heterogeneity, enabling the discovery of peptide ligands which selectively home to specific tissues. A prime example is identification of the iron-mimicking peptide CRTIGPSVC which undergoes receptor-mediated transport across the blood-brain barrier (BBB) by binding to the transferrin/transferrin receptor (TfR) complex. Various other brain-homing and BBB-crossing peptides have been discovered by in vivo phage display as well as phage display performed in vitro, i.e., in BBB models, cultured cells, and immobilized receptors. Furthermore, these peptides have been used for preclinical therapeutic applications for a number of different brain disorders. Continued research involving phage display is expected to further characterize the determinants of BBB transport, uncover additional BBB-crossing peptides, and facilitate ongoing development of brain-targeted therapies.