title: Development of gene-based therapies for cartilage repair.
abstract: Articular cartilage is particularly vulnerable to injury and degenerative conditions, and has a limited capacity for self-repair. Although current clinical procedures cannot restore a normal articular surface, there are a growing number of proteins that may be used to augment a repair process, or protect cartilage from degeneration. Because proteins are often difficult to administer effectively, gene therapy approaches are being developed to provide their sustained synthesis at sites of injury or disease. To promote cartilage repair, cDNAs can be targeted to synovium, or cartilage. Gene transfer to the synovium is generally considered more suitable for chondroprotective therapies that rely on expression of large amounts of anti-inflammatory mediators. The delivery of genes to cartilage defects to promote enhanced repair can be performed by either direct administration of gene delivery vectors, or by implantation of genetically modified chondrogenic cells. Variations of these methods have been used to demonstrate that exogenous cDNAs encoding growth factors can be delivered locally to sites of cartilage damage where they are expressed at physiologically relevant levels. Data is beginning to emerge that suggests that delivery and expression of these genescan influence a repair response toward the synthesis of normal articular cartilage in vivo. This article reviews the current status of gene delivery for cartilage healing and presents some of the remaining challenges.
authors.affiliation: Center for Molecular Orthopaedics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Glyn
authors.initials: G
authors.lastname: Palmer
authors.forename: Arnulf
authors.initials: A
authors.lastname: Pascher
authors.forename: Elvire
authors.initials: E
authors.lastname: Gouze
authors.forename: Jean-Noel
authors.initials: JN
authors.lastname: Gouze
authors.forename: Oliver
authors.initials: O
authors.lastname: Betz
authors.forename: Myron
authors.initials: M
authors.lastname: Spector
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Evans
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ghivizzani
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000502:physiology* / Q000601:surgery; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics; D012038:Regeneration / Q000235:genetics*
chemical_list: D011994:Recombinant Proteins