ADENOVIRUS-MEDIATED GENE DELIVERY TO THE JOINTS OF GUINEA-PIGS

Objective. To clarify in vivo applicability of adenovirus mediated gen e delivery to examine a gene therapy for human joint diseases. Methods . We directly injected vectors harbouring beta-galactosidase gene and transforming growth factor (TGF)-beta 1 gene into the joints of Hartle y guinea pigs. Expressions of delivered LacZ were examined by 5-bromo- 4-chloro-3-indolyl-beta-D-galactoside staining and reverse transcripti on-polymerase chain reaction. The levels of TGF-beta 1 that mere deliv ered to the joint and then transferred to the joint fluid were assesse d by ELISA. Results. LacZ expression was observed in almost all synovi al tissue samples and in chondrocytes on the surface of degenerated ca rtilage. In the other organs, expression of delivered genes was not ob served. For 2 weeks following gene delivery TGF-beta 1 levels in joint fluid were significantly higher than the levels in the controls for 2 weeks. Conclusion. Direct gene delivery into the joint cavity is feas ible with the in vivo gene delivery method using adenovirus vector and would be clinically applicable.