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Oligonucleotides can be directly delivered 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 [Ref.: 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]. 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 fits 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.

Key features:

  • Modification to enhance cell delivery of an oligonucleotide
  • Used to add a N-acetylgalactosamine (GalNAc) residue to the 3' or 5’ end of an oligonucleotide, or internally
  • GalNAc ligand supplied either as CPG or phosphoramidite
  • dR functionality conforms to natural sugar-phosphate backbone
  • Alpha anomer is nuclease resistant
  • Beta anomer is not nuclease resistant
  • Allows multiple additions of GalNAc residues into an oligonucleotide
  • GalNAc-residues can be added multiple times to an oligo either internally or at the 3’ or 5’ termini
  • 500 Å CPG suitable for high yield applications such as therapeutic oligos (≤ 30mers)
  • 1000 Å CPG suitable for highly modified oligonucleotides (> 20mers)
  • Used for the delivery of siRNAs, ASOs, saRNAs, and anti-microRNAs
  • C6 spacer / Succinyl linker on CPG

  1. Description Add to basket
  2. dR-GalNAc (Alpha) CPG 1000 Å
  3. View Product Details >

      Pack Size Catalogue No Price Quantity
      100mg LK2440-B100 £77.86
      1g LK2440-C001 £356.43
      10x0.2μmol ALL-FIT LK2440-P002 £156.43
      10x1μmol ALL-FIT LK2440-P008 £235.00
      10x0.2µmol MerMade LK2440-P016 £156.43
      10x1µmol MerMade LK2440-P022 £235.00
  4. dR-GalNAc (Alpha) CPG 500 Å
  5. View Product Details >

      Pack Size Catalogue No Price Quantity
      100mg LK2489-B100 £77.86
      1g LK2489-C001 £356.43
      10x0.2μmol ALL-FIT LK2489-P002 £156.43
      10x1μmol ALL-FIT LK2489-P008 £235.00
      10x0.2µmol MerMade LK2489-P016 £156.43
      10x1µmol MerMade LK2489-P022 £235.00
  6. dR-GalNAc (Beta) Phosphoramidite
  7. View Product Details >

      Pack Size Catalogue No Price Quantity
      100µmol LK2568-F100 £227.86
      250mg LK2568-B250 £449.29