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Regional gene therapy for full‐thickness articular cartilage lesions using naked DNA with a collagen matrix
Author(s) -
Di Cesare Paul E.,
R. Frenkel Sally,
Carlson Cathy S.,
Fang Carrie,
Liu Chuanju
Publication year - 2006
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20143
Subject(s) - naked dna , plasmid , cartilage , genetic enhancement , transfection , microbiology and biotechnology , immunostaining , mesenchymal stem cell , complementary dna , gene delivery , type ii collagen , chemistry , gene , biology , anatomy , immunology , biochemistry , immunohistochemistry
A novel gene therapy approach for treating damaged cartilage is proposed that involves placing endotoxin‐free cDNA containing the gene for bone morphogenetic protein‐2 (BMP‐2) in type I collagen sponges and then transferring the naked plasmid DNA construct to the injury site. A full‐thickness cartilaginous defect in rabbits implanted with plasmid containing a marker gene (β‐galactosidase) showed expressed protein as detected by immunostaining. At 1 week postimplantation, mesenchymal cells subjacent to the defect had incorporated the implanted naked plasmid DNA and, once transfected, served as local bioreactors, transiently producing the gene product. Plasmids containing the gene for BMP‐2 implanted in collagen sponges in cartilage lesions stimulated hyalinelike articular cartilage repair at 12 weeks postimplantation, nearly equivalent in quality to that induced by collagen sponges with recombinant BMP‐2 protein. Our approach circumvents the risks of inflammation and immunogenic response associated with the use of viral vectors. Naked plasmid DNA as a vehicle for transferring therapeutic genes has been shown to be effective in a therapeutic model within rabbit articular cartilage and appears to be safe and cost effective. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res