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

Chem Commun (Camb). 2020 Jul 11;56(54):7439-7442. doi: 10.1039/d0cc02548h. Epub 2020 Jun 4.

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.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / metabolism
  • Cell Line
  • Endocytosis
  • Fluorescent Dyes / chemistry
  • Gene Silencing*
  • Humans
  • Maleimides / chemistry*
  • Mice
  • Microscopy, Confocal
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / metabolism*
  • Phosphates / chemistry
  • Rats

Substances

  • Biocompatible Materials
  • Fluorescent Dyes
  • Maleimides
  • Oligonucleotides, Antisense
  • Phosphates
  • phosphorodithioic acid