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RNA aptamers are of significant therapeutic and clinical interest because their activity can be easily reversed in vivo\u2014a useful feature that is difficult to achieve using other therapeutic modalities. Despite their therapeutic promise, RNA aptamers are limited by their poor blood circulation. The attachment of polyethylene glycol (PEG) to RNA aptamers addresses this limitation. However, an RNA aptamer\u2010PEG conjugate that is a reversible anticoagulant fails in a clinical trial due to the reactivity of the conjugate with pre\u2010existing PEG antibodies and has cast a pall over PEGylation of aptamers and other biologics, despite its long history of utility in drug delivery. Here, PEG antibody\u2010reactivity of this RNA aptamer is eliminated by conjugating it to a next\u2010generation PEG\u2010like brush polymer\u2014poly[(oligoethylene glycol) methyl ether methacrylate)] (POEGMA). The conjugate retained the drug's therapeutic action and the ability to be easily reversed. Importantly, this conjugate does not bind pre\u2010existing PEG antibodies that are prevalent in humans and does not induce a humoral immune response against the polymer itself in mice. These findings suggest a path to rescuing the PEGylation of RNA therapeutics and vaccines from the deleterious side\u2010effects of PEG.<\/jats:p>","DOI":"10.1002\/adma.202107852","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T21:19:48Z","timestamp":1641503988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["PEG\u2010Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4663-5215","authenticated-orcid":false,"given":"Imran","family":"Ozer","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Pitoc","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke 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