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Covalent coupling of polyethylene glycol (PEG) to protein drugs addresses this limitation. However, unlike previously thought, PEG is immunogenic. In addition to induced PEG antibodies, \u224870% of the US population has pre\u2010existing anti\u2010PEG antibodies. Both induced and preexisting anti\u2010PEG antibodies result in accelerated drug clearance, reduced clinical efficacy, and severe hypersensitivity reactions that have limited the clinical utility of uricase, an enzyme drug for treatment for refractory gout that is decorated with a PEG corona. Here, the authors synthesize a poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) conjugate of uricase that decorates the protein with multiple polymer chains to create a corona to solve these problems. The resulting uricase\u2010POEGMA is well\u2010defined, has high bioactivity, and outperforms its PEG counterparts in its pharmacokinetics (PK). Furthermore, the conjugate does not induce anti\u2010POEGMA antibodies and is not recognized by anti\u2010PEG antibodies. These findings suggest that POEGMA conjugation may provide a solution to the immunogenicity and antigenicity limitations of PEG while improving upon its PK benefits. These results transcend uricase and can be applied to other PEGylated therapeutics and the broader class of biologics with suboptimal PK.<\/jats:p>","DOI":"10.1002\/advs.202103672","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T04:45:23Z","timestamp":1644295523000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Polyethylene Glycol\u2010Like Brush Polymer Conjugate of a Protein Drug Does Not Induce an Antipolymer Immune Response and Has Enhanced Pharmacokinetics than Its Polyethylene Glycol Counterpart"],"prefix":"10.1002","volume":"9","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":"Garrett","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renpeng","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Zakharov","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parul","family":"Sirohi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita K.","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University School of Medicine  Durham NC 27710 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel H.","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Hershfield","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Rheumatology Duke University Medical Center  Durham NC 27710 USA"},{"name":"Department of Biochemistry Duke University School of Medicine  Durham NC 27710 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus M.","family":"Hucknall","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Chilkoti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Duke University  Durham NC 27708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2399"},{"key":"e_1_2_9_2_1","unstructured":"Global Markets for Bioengineered Protein Drugs. 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