{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:17:38Z","timestamp":1781104658155,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1994,1,4]]},"abstract":"<jats:p>A chimeric protein capable of binding and neutralizing tumor necrosis factor (TNF) and lymphotoxin was expressed in mice transduced with a replication-incompetent adenoviral vector into which a TNF inhibitor gene had been engineered. Within 3 days following the injection of 10(9) infectious particles, the TNF inhibitor concentration exceeded 1 mg\/ml of plasma; this level of expression was maintained for at least 4 weeks, and detectable TNF inhibitory activity was measured 6 weeks after injection of the recombinant virus. Introduction of the artificial gene produced a phenotypic effect comparable to homozygous deletion of the 55-kDa TNF receptor, in that animals were rendered highly susceptible to infection by Listeria monocytogenes, whereas control animals receiving a replication-incompetent virus coding for beta-galactosidase were capable of resisting Listeria challenge. Adenovirus-mediated transfer of a gene encoding a TNF inhibitor offers a practical means of imposing effective, long-term blockade of TNF activity in vivo for investigational and therapeutic purposes.<\/jats:p>","DOI":"10.1073\/pnas.91.1.215","type":"journal-article","created":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T20:29:48Z","timestamp":1149193788000},"page":"215-219","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":164,"title":["Prolonged and effective blockade of tumor necrosis factor activity through adenovirus-mediated gene transfer."],"prefix":"10.1073","volume":"91","author":[{"given":"J","family":"Kolls","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, University of Texas, Southwestern Medical Center, Dallas 75235-9050."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Peppel","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of Texas, Southwestern Medical Center, Dallas 75235-9050."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Silva","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of Texas, Southwestern Medical Center, Dallas 75235-9050."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Beutler","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of Texas, Southwestern Medical Center, Dallas 75235-9050."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1994,1,4]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.91.1.215","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:37:49Z","timestamp":1649857069000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.91.1.215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,1,4]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1994,1,4]]}},"alternative-id":["10.1073\/pnas.91.1.215"],"URL":"https:\/\/doi.org\/10.1073\/pnas.91.1.215","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,1,4]]},"assertion":[{"value":"1994-01-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}