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However, its production depends on the farming of over a billion large animals annually, posing sustainability challenges, especially amidst increasing efforts to mitigate greenhouse gas (GHG) emissions by reducing animal farming. The rising demand for UFH has outpaced its supply, and previous attempts to develop synthetic alternatives have fallen short because of their limited potency and reversibility. Here, HD1\u201012dmA\u2010DAB is presented, a novel synthetic anticoagulant developed through chemical conjugation of a thrombin exosite\u2010binding aptamer (HD1) with a thrombin active\u2010site inhibitor (dabigatran). By optimizing dual\u2010site synergistic binding, HD1\u201012dmA\u2010DAB achieves an enhancement of over three orders of magnitude in thrombin\u2010binding affinity and specificity compared to HD1 alone. It also demonstrates superior plasma stability and anticoagulant efficacy comparable to UFH, as validated in in vitro, in vivo, and ex vivo clotting models. This breakthrough highlights a promising step toward a sustainable, animal\u2010free alternative to UFH, addressing the growing clinical demand and advancing environmental sustainability objectives.<\/jats:p>","DOI":"10.1002\/advs.202509867","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T03:11:43Z","timestamp":1759806703000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Aptamer\u2010Based EXACT Anticoagulant as a Sustainable, Animal\u2010Free Alternative to Unfractionated Heparin"],"prefix":"10.1002","volume":"13","author":[{"given":"Haixiang","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Surgery Duke University  Durham NC 27710 USA"},{"name":"Department of Biochemistry School of Life Science and Technology China Pharmaceutical University  Nanjing 211198 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Pitoc","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine Duke University  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Clancy","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Francis","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine Duke University Hospital  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Sullenger","sequence":"additional","affiliation":[{"name":"School of Medicine Duke University  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Rempel","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susannah","family":"Gammell","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jillian","family":"Caiazzi","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University  Durham NC 27710 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-5541","authenticated-orcid":false,"given":"Bruce A.","family":"Sullenger","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University  Durham NC 27710 USA"},{"name":"Departments of Pharmacology &amp; 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