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Adenovirus mediated gene delivery to the joints of guinea pigs
1Department of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, Japan.
Objective:
To clarify in vivo applicability of adenovirus mediated gene delivery to examine a gene therapy for human joint diseases.
Methods:
We directly injected vectors harbouring beta-galactosidase gene and transforming growth factor (TGF)-beta1 gene into the joints of Hartley guinea pigs. Expressions of delivered LacZ were examined by 5-bromo-4-chloro-3-indolyl-beta-D-galactoside staining and reverse transcription-polymerase chain reaction. The levels of TGF-beta1 that were delivered to the joint and then transferred to the joint fluid were assessed by ELISA.
Results:
LacZ expression was observed in almost all synovial tissue samples and in chondrocytes on the surface of degenerated cartilage. In the other organs, expression of delivered genes was not observed. For 2 weeks following gene delivery TGF-beta1 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 feasible with the in vivo gene delivery method using adenovirus vector and would be clinically applicable.