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

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.