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While increasingly PEGylated protein drugs have been approved by the FDA, the non\u2010degradability of PEG and the emergence of anti\u2010PEG antibodies after injection raise concerns about their cumulative chronic toxicity and long\u2010term therapeutic efficacy. Zwitterionic polymer, with a unique structure containing equal amounts of positively charged and negatively charged groups, shows a different hydration behavior to PEG, which may be a superior PEG alternative for protein conjugation. In this concept review, a series of features beyond that of PEGylated protein exhibited by protein\u2010zwitterionic polymer conjugate are discussed and some suggestions are presented for their future direction.<\/jats:p>","DOI":"10.1002\/cmdc.202300245","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T04:44:41Z","timestamp":1694061881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Zwitterionic Polymer: A New Paradigm for Protein Conjugation beyond PEG"],"prefix":"10.1002","volume":"18","author":[{"given":"Zhipeng","family":"Zeng","sequence":"first","affiliation":[{"name":"Center for Nanomedicine The Third Affiliated Hospital Sun Yat-sen University  Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Functional Biomaterials Key Laboratory of Polymeric 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