Homing peptides are useful for in vivo labeling and nonviral gene transfer to selective tissues and cell types. The aim of this project was to develop a renal collecting duct homing peptide. Using phage display, we identified a phage expressing a cyclic 7 amino acid peptide, which was internalized in a collecting duct cell line. Moreover, the phage was internalized in the collecting duct cells after i.v. injection in mice. To test if the peptide could be used for nonviral gene transfer, we synthesized the identified peptide fused to a protamine fragment. The fusion pep-tide was able to bind plasmid GFP cDNA and when the peptide/cDNA complex was injected

i.p. in mice, GFP expression was detected in the collecting duct cells. However, GFP expression level was very low. In order to track the fate of the peptide in vivo, we synthesized a FITC labeled version of the identified peptide. Using in vivo multiphoton imaging, we found that the FITC labeled peptide was internalized in the collecting duct cells in both mice and rats. However, the peptide labeled the cells in a punctuated pattern, indicating that peptide is not able to escape the endosomes after internalization. Together, our data indicate that we have developed a peptide, which can be used to label the collecting duct cells in mice and rats; however, further development is needed in order to use the peptide as a vector for nonviral gene transfer in vivo.