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Grafting multi-maleimides on antisense oligonucleotide to enhance its cellular uptake and gene silencing capability
Yuanyuan Guo1, Jiao Zhang, Gaifang Pan
1School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. chuanzhang@sjtu.edu.cn.
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.
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