Adenovirus mediated gene delivery to the joints of guinea pigs.
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.


CONCLUSIONS
Direct gene delivery into the joint cavity is feasible with the in vivo gene delivery method using adenovirus vector and would be clinically applicable.
Ikeda
T
T
Department of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, Japan.
Kubo
T
T
Arai
Y
Y
Nakanishi
T
T
Kobayashi
K
K
Takahashi
K
K
Imanishi
J
J
Takigawa
M
M
Hirasawa
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002356:Cartilage / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006168:Guinea Pigs; D007719:Knee Joint / Q000378:metabolism; D007763:Lac Operon; D010003:Osteoarthritis / Q000473:pathology / Q000628:therapy*; D013583:Synovial Membrane / Q000378:metabolism; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D016212:Transforming Growth Factor beta