Synthesis of galNAc-oligonucleotide conjugates using galnac phosphoramidite and triple-galNAc CPG solid support

Egor A. Ulashchik, Yury V. Martynenko-Makaev, Tatsiana P. Akhlamionok, Denis M. Melnik, Vadim V. Shmanai, Timofei S. Zatsepin

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Citation (Scopus)

Abstract

GalNAc oligonucleotide conjugates demonstrate improved potency in vivo due to selective and efficient delivery to hepatocytes in the liver via receptor-mediated endocytosis. GalNAc-siRNA and GalNAc-antisense oligonucleotides are at various stages of clinical trials, while the first two drugs were already approved by FDA. Also, GalNAc conjugates are excellent tools for functional genomics and target validation in vivo. The number of GalNAc residues in a conjugate is crucial for delivery as cooperative interaction of several GalNAc residues with asialoglycoprotein receptor enhances delivery in vitro and in vivo. Here we provide a robust protocol for the synthesis of triple GalNAc CPG solid support and GalNAc phosphoramidite, synthesis and purification of RNA conjugates with multiple GalNAc residues either to 5′-end or 3′-end and siRNA duplex formation.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages101-118
Number of pages18
DOIs
Publication statusPublished - 2021

Publication series

NameMethods in Molecular Biology
Volume2282
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • CPG
  • GalNAc
  • N-Acetylgalactosamine
  • Phosphoramidite
  • RNA

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