title: Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display.
abstract: Gene therapy is a promising method for osteoarthritis and cartilage injury. However, specifically delivering target genes into chondrocytes is a great challenge because of their non-vascularity and the dense extracellular matrix of cartilage. In our study, we identified a chondrocyte-affinity peptide (CAP, DWRVIIPPRPSA) by phage display technology. Subsequent analysis suggests that the peptide can efficiently interact specifically with chondrocytes without any species specificity. Polyethylenimine (PEI) was covalently modified with CAP to construct a non-viral vector for cartilage-targeted therapy. To investigate the cartilage-targeting property of the CAP-modified vector, FITC-labeled CAP conjugated PEI/DNA particles were injected into rabbit knee joints, and visualized under confocal microscope. Higher concentrations of CAP-modified vector were detected in the cartilage and specifically taken up by chondrocytes compared with a randomly scrambled peptide (SP)-modified vector. To evaluate cartilage-targeting transfection efficiency, the GFP and luciferase genes were delivered into knee joints using CAP- and SP-modified PEI. Cartilage transfections mediated by CAP-modified PEI were much more efficient and specific than those by SP-modified PEI. This result suggests that CAP-modified PEI could be used as a specific cartilage-targeting vector for cartilage disorders.
authors.affiliation: Institute of Sports Medicine, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100083, PR China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Pi
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Junjun
authors.initials: J
authors.lastname: Shi
authors.forename: Jinxian
authors.initials: J
authors.lastname: Zhu
authors.forename: Wenqing
authors.initials: W
authors.lastname: Chen
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zhang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
authors.forename: Yingfang
authors.initials: Y
authors.lastname: Ao
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011817:Rabbits
chemical_list: D019151:Peptide Library; D010455:Peptides; D011094:Polyethyleneimine