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However, the efficient and targeted delivery of siRNA remains a major challenge due to issues with tissue specificity and degradation in vivo. In this study, A DNA origami\u2010based chondrocyte\u2010targeted delivery system (OCS) is designed for siRNA delivery to OA\u2010affected cartilage. The DNA origami is engineered to load with siRNA targeting signal transducer and activator of transcription 3 (Stat3), a key regulator of inflammation and cartilage degradation, and is functionalized with anti\u2010CD44 aptamers for selective targeting of OA chondrocytes. In vitro, the DNA origami system effectively delivers siRNA to diseased chondrocytes, silencing matrix metalloproteinases expression and reducing inflammation. In OA rat models, it preserves cartilage integrity, promotes regeneration, and mitigates ECM degradation without evident side effects. These findings highlight DNA origami as a promising platform for siRNA\u2010based OA therapy, offering a promising solution to the challenges of targeted and efficient siRNA delivery.<\/jats:p>","DOI":"10.1002\/advs.202503939","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T10:40:48Z","timestamp":1747824048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["DNA Origami\u2010Based CD44\u2010Targeted Therapy Silences Stat3 Enhances Cartilage Regeneration and Alleviates Osteoarthritis Progression"],"prefix":"10.1002","volume":"12","author":[{"given":"Qi","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Medical Imaging Tongji Hospital School of Medicine Tongji University  Shanghai 200065 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Surgery of Spine 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