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There remains a need for local therapies that, following a single injection, can provide long-term pain relief and functional improvement and potentially delay disease progression. FX201 is a novel, intra-articular (IA), interleukin-1 receptor antagonist (IL-1Ra) gene therapy in development for the treatment of OA. In this study, we assessed the efficacy, biodistribution, and safety of helper-dependent adenovirus (HDAd)-ratIL-1Ra, the rat surrogate of FX201, and the biodistribution of FX201, in the anterior cruciate ligament transection (ACLT) rat OA model. A single IA injection of HDAd-ratIL-1Ra administered 7 days post-ACLT mitigated OA-related changes to cartilage, bone, and the synovial membrane at week 12 following surgery. Furthermore, FX201 and HDAd-ratIL-1Ra persisted for at least 92 days in the injected joint and proximal tissues with minimal evidence of vector spreading peripherally. Finally, HDAd-ratIL-1Ra showed a favorable safety profile without any local or systemic adverse effects. In conclusion, HDAd-ratIL-1Ra demonstrated local therapeutic and disease-modifying effects and was well tolerated, supporting further clinical development of FX201.<\/jats:p>","DOI":"10.1089\/hum.2021.131","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T04:35:09Z","timestamp":1640752509000},"page":"541-549","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["Efficacy and Safety of FX201, a Novel Intra-Articular IL-1Ra Gene Therapy for Osteoarthritis Treatment, in a Rat Model"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5650-1187","authenticated-orcid":false,"given":"Rebecca","family":"Senter","sequence":"first","affiliation":[{"name":"Flexion Therapeutics, Inc., ,  Burlington, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogely","family":"Boyce","sequence":"additional","affiliation":[{"name":"Beechy Ridge ToxPath, LLC, Clay, West Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Repic","sequence":"additional","affiliation":[{"name":"MC Toxicology Consulting, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Walsh","family":"Martin","sequence":"additional","affiliation":[{"name":"Tremont Therapeutics, LLC, Charlestown, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Chabicovsky","sequence":"additional","affiliation":[{"name":"MC Toxicology Consulting, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Langevin-Carpentier","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Senneville, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"B\u00e9dard","sequence":"additional","affiliation":[{"name":"Charles River Laboratories, Senneville, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Bodick","sequence":"additional","affiliation":[{"name":"Gate Science, Inc., Moultonborough, New Hampshire, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.11.634"},{"key":"e_1_3_5_3_2","first-page":"376","article-title":"Clinical aspects, pathology and pathophysiology of osteoarthritis","volume":"6","author":"Goldring SR","year":"2006","unstructured":"Goldring SR, , Goldring MB. 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