{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:53:55Z","timestamp":1790870035094,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2007,5,21]],"date-time":"2007-05-21T00:00:00Z","timestamp":1179705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The tumor necrosis factor (TNF)\u2010\u03b1 plays a central role in rheumatoid arthritis (RA) and current biotherapies targeting TNF\u2010\u03b1 have a major impact on RA treatment. The long\u2010term safety concerns associated with the repetitive TNF blockade prompt optimization of therapeutic anti\u2010TNF approaches. Since we recently demonstrated that intra\u2010articular gene transfer using a recombinant adeno\u2010associated virus serotype 5 (rAAV5) efficiently transduces arthritic joints, we evaluate its effect on collagen\u2010induced arthritis (CIA) when encoding TNF antagonists.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Recombinant AAV5 vectors encoding the human TNFRp55 extracellular domain fused to the Fc region of mice IgG1 (TR1) or a small molecular weight dimeric human TNFRp75 extracellular domain (TR2), under two different promoters, the CMV or a chimeric NF\u2010\u03baB\u2010based promoter inducible by inflammation, were injected into mouse CIA joints.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Best protection against arthritis was obtained with the rAAV5 encoding the TR1, as reflected by delayed disease onset, decreased incidence and severity of joint damage. This effect was associated with a transient expression of the anti\u2010TNF agent when expressed under a NF\u2010\u03baB\u2010responsive promoter, only detectable during disease flare, while the antagonist expression was rapidly increased and stable when expressed from a CMV promoter. Importantly, using the intra\u2010articular administration of the rAAV5\u2010NF\u2010\u03baB\u2010TR1 vector, we observed a striking correlation between local TR1 expression and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings strongly support the feasibility of improving the safety of anti\u2010TNF approaches for the treatment of arthritis by local rAAV5\u2010mediated gene expression under an inflammation\u2010responsive promoter, able to provide a limited, transient and therapeutically relevant expression of anti\u2010TNF compounds. Copyright \u00a9 2007 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1053","type":"journal-article","created":{"date-parts":[[2007,5,21]],"date-time":"2007-05-21T09:51:06Z","timestamp":1179741066000},"page":"596-604","source":"Crossref","is-referenced-by-count":58,"title":["Inflammation\u2010inducible anti\u2010TNF gene expression mediated by intra\u2010articular injection of serotype 5 adeno\u2010associated virus reduces arthritis"],"prefix":"10.1002","volume":"9","author":[{"given":"M.","family":"Khoury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Adriaansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J. B. 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