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A Long‐Circulating Vector for Aptamers Based upon Polyphosphodiester‐Backboned Molecular Brushes

Wang, Yuyan ; Wang, Dali ; Lin, Jiachen ; Lyu, Zidi ; Chen, Peiru ; Sun, Tingyu ; Xue, Chenyang ; Mojtabavi, Mehrnaz ; Vedadghavami, Armin ; Zhang, Zheyu ; Wang, Ruimeng ; Zhang, Lei ; Park, Christopher ; Heo, Gyu Seong ; Liu, Yongjian ; Dong, Sijia S. ; Zhang, Ke

Angewandte Chemie, 2022-10, Vol.134 (41), p.n/a [Peer Reviewed Journal]

Weinheim: Wiley Subscription Services, Inc

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Title:
A Long‐Circulating Vector for Aptamers Based upon Polyphosphodiester‐Backboned Molecular Brushes
Author: Wang, Yuyan ; Wang, Dali ; Lin, Jiachen ; Lyu, Zidi ; Chen, Peiru ; Sun, Tingyu ; Xue, Chenyang ; Mojtabavi, Mehrnaz ; Vedadghavami, Armin ; Zhang, Zheyu ; Wang, Ruimeng ; Zhang, Lei ; Park, Christopher ; Heo, Gyu Seong ; Liu, Yongjian ; Dong, Sijia S. ; Zhang, Ke
Subjects: Anticoagulant ; Aptamer ; Aptamers ; Biological activity ; Blood circulation ; Bottlebrush Polymer ; Chemistry ; Nuclease ; Oligonucleotides ; PEGylation ; Polyethylene glycol ; Polymers ; Solid phase methods ; Solid phase synthesis
Is Part Of: Angewandte Chemie, 2022-10, Vol.134 (41), p.n/a
Description: Aptamers face challenges for use outside the ideal conditions in which they are developed. These difficulties are most palpable in vivo due to nuclease activities, rapid clearance, and off‐target binding. Herein, we demonstrate that a polyphosphodiester‐backboned molecular brush can suppress enzymatic digestion, reduce non‐specific 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‐phase synthesis, followed by installation of poly(ethylene glycol) (PEG) side chains using a two‐step process with near‐quantitative 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‐based therapeutics. A bottlebrush polymer‐aptamer biohybrid, termed PSP pacDNA, is prepared using solid‐phase and graft‐onto methodologies. Consisting of a polyphosphodiester backbone and poly(ethylene glycol) side chains, the PSP pacDNA suppresses non‐specific interactions with the cell and improves the plasma pharmacokinetics of the aptamer. Combined with a thrombin‐binding aptamer, the PSP pacDNA produces a pronounced anticoagulation effect in vivo.
Publisher: Weinheim: Wiley Subscription Services, Inc
Language: English

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A Long‐Circulating Vector for Aptamers Based upon Polyphosphodiester‐Backboned Molecular Brushes

Wang, Yuyan ; Wang, Dali ; Lin, Jiachen ; Lyu, Zidi ; Chen, Peiru ; Sun, Tingyu ; Xue, Chenyang ; Mojtabavi, Mehrnaz ; Vedadghavami, Armin ; Zhang, Zheyu ; Wang, Ruimeng ; Zhang, Lei ; Park, Christopher ; Heo, Gyu Seong ; Liu, Yongjian ; Dong, Sijia S. ; Zhang, Ke

Weinheim: Wiley Subscription Services, Inc

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