S. Watanabe et al., Adeno-associated virus mediates long-term gene transfer and delivery of chondroprotective IL-4 to murine synovium, MOL THER, 2(2), 2000, pp. 147
Treatments for rheumatoid arthritis and other inflammatory arthropathies ar
e often ineffective at preventing joint destruction. Long-term genetic modi
fication of the cells lining the joint space (synoviocytes) in vivo represe
nts a potential method for the treatment of these chronic conditions. Howev
er, a vector capable of efficiently transducing synoviocytes in vivo for a
persistent period has not been available. The present report describes the
genetic modification of synoviocytes in vivo using recombinant adeno-associ
ated virus. High-titer adeno-associated virus encoding the gene for Escheri
chia coil beta -galactosidase was injected into the knee joints of mice. Sy
novial tissues were then examined for beta -galactosidase transgene express
ion by in situ staining and by fluorometry. High-efficiency, persistent tra
nsgene expression was observed in the synovium with no evidence of vector-i
nduced inflammation. Expression was observed for at least 7 months and was
higher in arthritic than nonarthritic mice. Gene transfer of murine IL-4 to
the joints of mice with collagen-induced arthritis led to detectable level
s of IL-4 in the joint and protection from articular cartilage destruction.
These data suggest that adeno-associated virus may be a useful vector for
gene delivery to the synovium for the treatment of inflammatory arthropathi
es.