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dR-GalNAc (Alpha) CPG

dR-GalNAc (Alpha) CPG

CPG for incorporation of GalNAc at 3' end of an oligonucleotide, with a dR spacer

Key features

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  • Modification to enhance cell delivery of an oligonucleotide (such as siRNAs, ASOs, saRNAs, and anti-microRNAs)
  • Used to add N-acetylgalactosamine (GalNAc) residue to the 3' end of an oligonucleotide
  • dR functionality conforms to natural sugar-phosphate backbone
  • Alpha anomer is nuclease resistant
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Option 2: Select a Functional Loading
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Product information

Oligonucleotide therapeutics have the potential to treat a myriad of different diseases, however, their efficient delivery to targeted cells and organs remains extremely challenging. Their high molecular size and anionic backbone hinder their cellular uptake. In addition, unmodified oligonucleotides are prone to endonucleases degradation, rapid elimination from the systemic circulation, and can trigger an immune response. Various delivery technologies have been developed to improve oligonucleotides cell delivery, including viral and non-viral carriers, and direct conjugation of oligonucleotides to ligand moieties, such as lipids. One approach is to deliver oligonucleotides directly to the liver by targeting the asialoglycoprotein receptor (ASGPR), which is highly expressed in the membrane of hepatocytes. This is done by decorating oligonucleotides with a cluster of N-acetylgalactosamine (GalNAc) residues. The affinity of ASGPR for a trimer of GalNAc has been shown to be 1,000-fold higher than for a dimer or monomer and only slightly lower than for a tetramer (1). GalNAc-decorated oligonucleotides bind to the ASGPR, which triggers their rapid engulfment in endosomes. GalNAc sugars are then lysed from the oligonucleotide, allowing this latter to escape to the cytoplasm by a still poorly understood mechanism, where it induces an RNAi response. We are glad to offer you a GalNAc phosphoramidite (LK2568) and two equivalent GalNAc solid supports, with a choice between two different pore sizes (LK2440 and LK2489). Our GalNAc monomers can be used to build up flexible GalNAc clusters, varying in the number of GalNAc monomers and in their position within the oligo. Additionally, it is possible to add various spacers between each GalNAc monomer and to incorporate cleavable linkers between the oligo and the GalNAc cluster. Our GalNAc products LK2568, LK2440 and LK2489, have a dR moiety which wits directly into the natural sugar phosphate backbone with little disruption of the duplex, meaning there is minimal effect on the Tm. In these products, modifications on the dR backbone show nuclease resistance with α-anomer, but not with the β-anomer.


  1. Lee, Y.C., and Lee, R.T. (2008). Interactions of oligosaccharides and glycopeptides with hepatic carbohydrate receptors. In Carbohydrates in Chemistry and Biology: A Comprehensive Handbook, B. Ernst, G.W. Hart, and P. Sinaÿ, eds. (Wiley),pp. 549–561

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