Basic Research of Gene Therapy for Joint Diseases

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We evaluated the in vivo applicability of adenovirus-mediated gene delivery in order to consider the feasibility of gene therapy for human joint diseases.We directly injected vectors harbouring beta-galactosidase (beta-gal) or transforming growth factor (TGF)-beta1 gene into the joints of Hartley guinea pigs. Expressions of transduced beta-gal genes were examined by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining and reverse transcription- polymerase chain reaction (RT-PCR). The levels of TGF-beta1 which was delivered to the joint and then transferred to the joint fluid, were assessed by enzyme-linked immunosorbent assay (ELISA). LacZ expression was observed in almost the entire synovial tissues and in chondrocytes on the surface of degenerated cartilage. Un expected effects of the direct vector inj ection on the other organs were also examined, no expression of delivered gene was observed. Therefore, intraarticular direct injection would achieve gene delivery limited to the joint cavity, possibly eliminating unecessary systemic effects. TGF-beta1 levels in the joint fluid following the gene delivery had been significantly higher than the levels in the controls for 2 weeks.Direct gene delivery into the joint cavity is realistic with the in vivo gene delivery method using adenovirus vector, and it would be clinically applicable.