{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:40:40Z","timestamp":1791492040678,"version":"4.3.4"},"reference-count":103,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>\n                    Most forms of arthritis are incurable, difficult to treat, and a major cause of disability in Western countries. Better local treatment of arthritis is impaired by the pharmacokinetics of the joint that make it very difficult to deliver drugs to joints at sustained, therapeutic concentrations. This is especially true of biologic drugs, such as proteins and RNA, many of which show great promise in preclinical studies. Gene transfer provides a strategy for overcoming this limitation. The basic concept is to deliver cDNAs encoding therapeutic products by direct intra-articular injection, leading to sustained, endogenous synthesis of the gene products within the joint. Proof of concept has been achieved for both\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    gene delivery using a variety of vectors, genes, and cells in several different animal models. There have been a small number of clinical trials for rheumatoid arthritis (RA) and osteoarthritis (OA) using retrovirus vectors for\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    gene delivery and adeno-associated virus (AAV) for\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    delivery. AAV is of particular interest because, unlike other viral vectors, it is able to penetrate deep within articular cartilage and transduce chondrocytes\n                    <jats:italic toggle=\"yes\">in situ.<\/jats:italic>\n                    This property is of particular importance in OA, where changes in chondrocyte metabolism are thought to be fundamental to the pathophysiology of the disease. Authorities in Korea have recently approved the world's first arthritis gene therapy. This targets OA by the injection of allogeneic chondrocytes that have been transduced with a retrovirus carrying transforming growth factor-\u03b2\n                    <jats:sub>1<\/jats:sub>\n                    cDNA. Phase III studies are scheduled to start in the United States soon. Meanwhile, two additional Phase I trials are listed on\n                    <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/Clinicaltrials.gov\">Clinicaltrials.gov<\/jats:uri>\n                    , both using AAV. One targets RA by transferring interferon-\u03b2, and the other targets OA by transferring interleukin-1 receptor antagonist. The field is thus gaining momentum and promises to improve the treatment of these common and debilitating diseases.\n                  <\/jats:p>","DOI":"10.1089\/hum.2017.181","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T05:38:31Z","timestamp":1511242711000},"page":"2-14","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":127,"title":["Gene Delivery to Joints by Intra-Articular Injection"],"prefix":"10.1177","volume":"29","author":[{"given":"Christopher H.","family":"Evans","sequence":"first","affiliation":[{"name":"Mayo Clinic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Ghivizzani","sequence":"additional","affiliation":[{"name":"University of Florida College of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Robbins","sequence":"additional","affiliation":[{"name":"The Scripps Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,1,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23176"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24984"},{"key":"e_1_3_3_4_2","first-page":"578","article-title":"Impact of arthritis and multiple chronic conditions on selected life domains\u2014United States, 2013","volume":"64","author":"Qin J","year":"2015","unstructured":"Qin J, , Theis KA, , Barbour KE, et al. 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