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Cellular dysregulation can also lead to accumulation of endogenously produced dsRNA that stimulates a viral\u2010like immune response. Additionally, dsRNA contamination in RNA therapeutics can lead to harmful side effects via a similar pathway. Despite the clinical relevance of dsRNA, reliable tools for its detection remain limited. Currently, dsRNA detection relies almost exclusively on the monoclonal antibodies J2 and K1, which suffer from sequence bias and low sensitivity. To address this challenge, we repurposed naturally occurring dsRNA\u2010binding domains (dsRBDs) to produce reliable, pan\u2010specific affinity reagents for dsRNA. We systematically screened the dsRBDs of the three human adenosine deaminases acting on RNA (ADARs) and identified ADAR3 dsRBDs as the most promising candidates. We then engineered ADAR3\u2010derived dsRBD constructs having varying linker lengths and domain combinations to create dsRNA accumulation detected by ADAR3 RBDs (dsRADAR) affinity reagents. Finally, we demonstrate the superior performance of dsRADAR over currently available dsRNA antibodies in a cell model of viral infection and a tissue model of gastric inflammation. Together, dsRADAR provides a sensitive and reliable approach for imaging and detecting diverse dsRNA structures in biological contexts.<\/jats:p>","DOI":"10.1002\/anie.7655789","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:57:06Z","timestamp":1791356226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["dsRADAR: Imaging and Detecting Cellular dsRNA by Repurposing RNA\u2010Binding Proteins"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6061-8593","authenticated-orcid":false,"given":"Weina","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Chemistry Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9044-8313","authenticated-orcid":false,"given":"Tyson 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