Regional gene therapy for full-thickness articular cartilage lesions using naked DNA with a collagen matrix.
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 (beta-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.
Di Cesare
Paul E
PE
Musculoskeletal Research Laboratory, New York University-Hospital for Joint Diseases, Department of Orthopaedic Surgery, 301 East 17th Street, Suite 1500, New York 10003, USA. pedicesare@aol.com
Frenkel
Sally R
SR
Carlson
Cathy S
CS
Fang
Carrie
C
Liu
Chuanju
C
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002358:Cartilage, Articular / Q000293:injuries*; D003094:Collagen / Q000008:administration & dosage*; D004247:DNA / Q000008:administration & dosage*; D004058:Diffusion; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D010957:Plasmids; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000235:genetics*
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen; D004247:DNA