Issue 54, 2020
From the journal:

Chemical Communications

Grafting multi-maleimides on antisense oligonucleotide to enhance its cellular uptake and gene silencing capability†

Yuanyuan Guo,a   Jiao Zhang,a   Gaifang Pan,a   Chung Hang Jonathan Choi, ORCID logo b   Ping Wang,c   Yuehua Li,d   Xinyuan Zhu ORCID logo a  and  Chuan Zhang ORCID logo *a  

* Corresponding authors

a School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
E-mail: chuanzhang@sjtu.edu.cn

b Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

c Weigao Research Center, 304, Building 2, Lane 720, Cailun Rd., Shanghai, China

d Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600, Yi Shan Rd, Shanghai 200233, China

Abstract

A multitude of maleimides are grafted onto the backbone of a phosphorothioate antisense oligonucleotide (ASO) to generate the construct of maleimide-grafted ASO (Mal-g-ASO). Through click conjugation with cell membrane thiols that triggers endocytosis-independent cellular internalization, Mal-g-ASO exhibited enhanced cellular uptake efficiency, resulting in a remarkable improvement of ASO-based gene silencing.

Graphical abstract: Grafting multi-maleimides on antisense oligonucleotide to enhance its cellular uptake and gene silencing capability

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Article information

DOI
https://doi.org/10.1039/D0CC02548H
Article type
Communication
Submitted
08 Apr 2020
Accepted
14 May 2020
First published
14 May 2020

Chem. Commun., 2020,56, 7439-7442

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Grafting multi-maleimides on antisense oligonucleotide to enhance its cellular uptake and gene silencing capability

Y. Guo, J. Zhang, G. Pan, C. H. J. Choi, P. Wang, Y. Li, X. Zhu and C. Zhang, Chem. Commun., 2020, 56, 7439 DOI: 10.1039/D0CC02548H

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