In Vivo Selection and Validation of Liver-Specific Ligands Using a New T7 Phage Peptide Display System

Abstract

In vivo phage display is a powerful source of new peptide ligands for specific organ targeting by drugs and gene therapy vectors. Since the introduction of this methodology a decade ago, a number of peptides that preferentially react with organ-specific endothelium and parenchymal markers have been selected. One organ that has been conspicuously missing from these selection studies is the liver, which possesses a multitude of acquired and hereditary disorders and represents a highly important therapeutic target. Herein, we set out to fill this gap by introducing a novel peptide display system containing cloned sequences in the tail fiber protein (p17) of phage T7. The p17 display effectively avoids the innate immune system and is well suited both for selection of new liver-specific ligands and for validation of protein sequences that have been implicated in liver targeting by the use of conventional biochemical methods.