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MODERN RHEUMATOLOGY Vol.14 No.1
>MR14-1
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| Recombinant adeno-associated virus preferentially transduces human, compared to mouse, synovium: implications for arthritis therapy |
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| Shigeki Katakura1, Kristi Jennings1, Shohei Watanabe2, Eijiroh Adachi2, Sherry Thornton1, Guang-ping Gao3, James M. Wilson3, Haim Burstein4, Bruce Trapnell5 and Raphael Hirsch6 |
(1) William S. Rowe Division of Rheumatology, Childrens Hospital Medical Center, Cincinnati, OH, USA
(2) Department of Orthopaedic Surgery, Ehime University School of Medicine, Ehime, Japan
(3) Institute of Human Gene Therapy, University of Pennsylvania Health System, Philadelphia, PA, USA
(4) Targeted Genetics Corp., Seattle, WA, USA
(5) Division of Pulmonary Biology, Childrens Hospital Medical Center, Cincinnati, OH, USA
(6) Division of Rheumatology, Childrens Hospital of Pittsburgh, University of Pittsburgh, School of Medicine, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA |
Received: 23 July 2003 Accepted: 18 August 2003 |
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Abstract |
| Abstract Despite a number of published reports, including from our own laboratory, suggesting that adeno-associated virus (AAV) transduces mouse synovium, a careful analysis demonstrated transduction predominantly of the subsynovial muscle tissue, while the synovial lining is poorly transduced. To investigate the potential of AAV to transduce human synovium, three human rheumatoid arthritis (RA) and two murine collagen-induced arthritis (CIA) synovial cell lines were infected with recombinant AAV (rAAV) vectors encoding either mouse IL-10 or IL-4. Low-level transgene expression was observed. However, either -irradiation or the addition of a low-titer E1-, E3-deleted recombinant adenovirus resulted in up to a 100-fold increase in transgene product in the human, but not the mouse, cell lines. RA synovial tissues implanted subcutaneously in severe combined immunodeficiency (SCID) mice, which were subsequently infected with rAAV, showed marked increases in transgene expression when co-infected with adenovirus. To our knowledge, this is the first study to show that intact human synovial tissues can be transduced by rAAV, and it suggests that murine arthritis may not be an optimal model to study rAAV as a gene transfer vector. Further studies to elucidate the mechanisms limiting gene transduction in human synovium may allow optimization of this vector for the treatment of arthritis. |
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| Key words |
| Key words Adeno-associated virus (AAV) - Arthritis - Gene therapy - Synovium |
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