@article{bd41facb074f4d84ad1c137c8c1b69af,
title = "A Long-Circulating Vector for Aptamers Based upon Polyphosphodiester-Backboned Molecular Brushes",
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.",
keywords = "Anticoagulant, Aptamer, Bottlebrush Polymer, Oligonucleotides, PEGylation",
author = "Yuyan Wang and Dali Wang and Jiachen Lin and Zidi Lyu and Peiru Chen and Tingyu Sun and Chenyang Xue and Mehrnaz Mojtabavi and Armin Vedadghavami and Zheyu Zhang and Ruimeng Wang and Lei Zhang and Christopher Park and Heo, {Gyu Seong} and Yongjian Liu and Dong, {Sijia S.} and Ke Zhang",
note = "Funding Information: This work was supported by the National Institute of General Medical Sciences (1R01GM121612), the National Cancer Institute (1R01CA251730), and the National Science Foundation (DMR award number 2004947). We thank Prof. Meni Wanunu for the use of AFM, Prof. Ambika Bajpayee for the help on MST, Prof. Jiahe Li for the use of flow cytometer and Prof. Heather Clark for the use of in vivo imaging system. We also thank the Institute for Chemical Imaging of Living System at Northeastern University for instrument support. S.S.D. would like to thank Northeastern University for the startup funding and Northeastern University Research Computing for the computing resources. Funding Information: This work was supported by the National Institute of General Medical Sciences (1R01GM121612), the National Cancer Institute (1R01CA251730), and the National Science Foundation (DMR award number 2004947). We thank Prof. Meni Wanunu for the use of AFM, Prof. Ambika Bajpayee for the help on MST, Prof. Jiahe Li for the use of flow cytometer and Prof. Heather Clark for the use of in vivo imaging system. We also thank the Institute for Chemical Imaging of Living System at Northeastern University for instrument support. S.S.D. would like to thank Northeastern University for the startup funding and Northeastern University Research Computing for the computing resources. Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH.",
year = "2022",
month = oct,
day = "10",
doi = "10.1002/anie.202204576",
language = "English",
volume = "61",
journal = "Angewandte Chemie - International Edition",
issn = "1433-7851",
number = "41",
}