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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere202204576
JournalAngewandte Chemie - International Edition
Volume61
Issue number41
DOIs
StatePublished - Oct 10 2022

Keywords

  • Anticoagulant
  • Aptamer
  • Bottlebrush Polymer
  • Oligonucleotides
  • PEGylation

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