Mapping of vascular ZIP codes by phage display

Each organ and pathology has a unique vascular ZIP code that can be targeted with affinity ligands. In vivo peptide phage display can be used for unbiased mapping of the vascular diversity. Remarkably, some of the peptides identified by such screens not only bind to target vessels but also elicit biological responses. Recently identified tissue-penetrating CendR peptides trigger vascular exit and parenchymal spread of a wide range of conjugated and coadministered payloads. This review is designed to serve as a practical guide for researchers interested in setting up ex vivo and in vivo phage display technology. We focus on T7 coliphage platform that our lab prefers to use due to its versatility, physical resemblance of phage particles to clinical nanoparticles, and ease of manipulation.