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Identification of homing peptides specific for synovial microvascular endothelium using in vivo phage display selection

The microvascular endothelium (MVE) plays a major role in inflammation as well as tumour growth. Thus, the MVE represents an important therapeutic target. Peptide phage technology has been used in vivo to discover peptide sequences with binding capacity to organ specific MVE determinants in animals. The application of such powerful technology to humans has been limited by the obvious difficulties of performing phage-screening studies in vivo. By grafting human tissues into severe combined immunodeficient (SCID) mice, it is possible to target specifically human MVE determinants. Here we report for the first time the identification of synovial specific homing peptides by in vivo phage display selection in SCID mice transplanted with human synovium. Selected synovial homing peptide-phages were found to bind to human synovial graft MVE and retain their tissue homing specificity in vivo independently from phage component, disease origin of transplants and degree of human/murine graft vascularisation. In addition, the selected phages demonstrate tissue and species specificity in comparison to cotransplanted human skin grafts or mouse vasculature. Sequence analysis of the peptide inserts from synovial homing phages identified recurrent consensus motifs. One such motif maintains synovial MVE specificity both when expressed by a single phage-clone and as a free biotinylated synthetic peptide. Furthermore, the free peptide competes and inhibits, in vivo, the binding of the original peptide-phage to the cognate synovial MVE ligand. The identification of synovial homing peptides, with tissue and species specificity, may allow the construction of targeting devices capable of concentrating therapeutic/diagnostic materials to human joints.

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Lee, L., Buckley, C., Blades, M. et al. Identification of homing peptides specific for synovial microvascular endothelium using in vivo phage display selection. Arthritis Res Ther 4 (Suppl 1), 33 (2002).

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