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  • Title: Identification of synovium-specific homing peptides by in vivo phage display selection.
    Author: Lee L, Buckley C, Blades MC, Panayi G, George AJ, Pitzalis C.
    Journal: Arthritis Rheum; 2002 Aug; 46(8):2109-20. PubMed ID: 12209516.
    Abstract:
    OBJECTIVE: To identify homing peptides specific for human synovium that could be used as targeting devices for delivering therapeutic/diagnostic agents to human joints. METHODS: Human synovium and skin were transplanted into SCID mice. A disulfide-constrained 7-amino acid peptide phage display library was injected intravenously into the animals and synovial homing phage recovered from synovial grafts. Following 3-4 cycles of enrichment, DNA sequencing of homing phage clones allowed the identification of specific peptides that were synthesized by a-fluorenylmethyloxycarbonyl chemistry and used in competitive in vivo assays and immunohistochemistry analyses. RESULTS: We isolated synovial homing phages displaying specific peptides that distinctively bound to synovial but not skin or mouse microvascular endothelium (MVE). They retained their tissue homing specificity in vivo, independently from the phage component, the original pathology of the transplanted tissue, and the degree of human/murine graft vascularization. One such peptide (CKSTHDRLC) maintained synovial homing specificity both when presented by the phage and as a free synthetic peptide. The synthetic peptide also competed with and inhibited in vivo the binding of the parent phage to the cognate synovial MVE ligand. CONCLUSION: This is the first report describing peptides with homing properties specific for human synovial MVE. This was demonstrated using a novel approach targeting human tissues, transplanted into SCID mice, directly by in vivo phage display selection. The identification of such peptides opens the possibility of using these sequences to construct joint-specific drug delivery systems that may have considerable impact in the treatment of arthritic conditions.
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