Depending on their physiologic location and functional state, vascular endothelial cells express surface receptors differentially. Recognition of this molecular diversity is essential for the development of targeted therapies. Random phage display peptide libraries can be selected in vitro on recombinant proteins or on intact cells. After systemic injection, selection can be performed in animals and humans in vivo for the isolation of ligands for tissue-specific receptors. For the screening of libraries on intact cells or tissues, no a priori knowledge of the targeted receptor is needed, as the recovered peptide ligands can identify their corresponding receptors. Furthermore, the isolated peptides can be used to target therapeutic chemicals, biologicals, gene therapy vectors, or diagnostic compounds to specific tissues in vivo. Protocols for the screening of phage libraries in these three settings--on proteins, on cells in vitro and in the living animal--are described in this chapter.
Depending on their physiologic location and functional state, vascular endothelial cells express surface receptors differentially. Recognition of this molecular diversity is essential for the development of targeted therapies. Random phage display peptide libraries can be selected in vitro on recombinant proteins or on intact cells. After systemic injection, selection can be performed in animals and humans in vivo for the isolation of ligands for tissue-specific receptors. For the screening of libraries on intact cells or tissues, no a priori knowledge of the targeted receptor is needed, as the recovered peptide ligands can identify their corresponding receptors. Furthermore, the isolated peptides can be used to target therapeutic chemicals, biologicals, gene therapy vectors, or diagnostic compounds to specific tissues in vivo. Protocols for the screening of phage libraries in these three settings--on proteins, on cells in vitro and in the living animal--are described in this chapter.