Adeno-associated virus mediates long-term gene transfer and delivery of chondroprotective IL-4 to murine synovium

Mol Ther. 2000 Aug;2(2):147-52. doi: 10.1006/mthe.2000.0111.


Treatments for rheumatoid arthritis and other inflammatory arthropathies are often ineffective at preventing joint destruction. Long-term genetic modification of the cells lining the joint space (synoviocytes) in vivo represents a potential method for the treatment of these chronic conditions. However, 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-associated virus. High-titer adeno-associated virus encoding the gene for Escherichia coli beta-galactosidase was injected into the knee joints of mice. Synovial tissues were then examined for beta-galactosidase transgene expression by in situ staining and by fluorometry. High-efficiency, persistent transgene expression was observed in the synovium with no evidence of vector-induced 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 levels 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 arthropathies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis / therapy
  • Cartilage, Articular / pathology
  • Chondrocytes / metabolism
  • Dependovirus / genetics*
  • Escherichia coli / enzymology
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Interleukin-4 / genetics*
  • Interleukin-4 / therapeutic use
  • Male
  • Mice
  • Mice, Inbred DBA
  • Patella / metabolism
  • Proteoglycans / biosynthesis
  • Spectrometry, Fluorescence
  • Synovial Membrane / metabolism*
  • Time Factors
  • Transgenes
  • beta-Galactosidase / metabolism


  • Proteoglycans
  • Interleukin-4
  • beta-Galactosidase