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These difficulties are most palpable in vivo due to nuclease activities, rapid clearance, and off\u2010target binding. Herein, we demonstrate that a polyphosphodiester\u2010backboned molecular brush can suppress enzymatic digestion, reduce non\u2010specific cell uptake, enable long blood circulation, and rescue the bioactivity of a conjugated aptamer in vivo. The backbone along with the aptamer is assembled via solid\u2010phase synthesis, followed by installation of poly(ethylene glycol) (PEG) side chains using a two\u2010step process with near\u2010quantitative efficiency. The synthesis allows for precise control over polymer size and architecture. Consisting entirely of building blocks that are generally recognized as safe for therapeutics, this novel molecular brush is expected to provide a highly translatable route for aptamer\u2010based therapeutics.<\/jats:p>","DOI":"10.1002\/anie.202204576","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T04:54:13Z","timestamp":1660798453000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A Long\u2010Circulating Vector for Aptamers Based upon Polyphosphodiester\u2010Backboned Molecular Brushes"],"prefix":"10.1002","volume":"61","author":[{"given":"Yuyan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Biology Northeastern University  Boston MA 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dali","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology 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