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Tri-GalNAc-TEG C7 CPG

Tri-GalNAc-TEG C7 CPG

CPG used to add a trivalent GalNAc ligand to the 3' end of an oligonucleotide.

Key features

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  • Modification to enhance cell delivery.
  • CPG has a long-chain alkylamino succinyl linker.
  • Contains a DMT functionality.
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Product information

Oligonucleotide Therapeutics

Oligonucleotide Therapeutics

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. 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.

In addition to our monomeric GalNAc ligands (dR-GalNAc (Beta) Phosphoramidite, LK2568) and (dR-GalNAc (Alpha) CPG (LK2440 and LK2489), we now also offer a triantennary GalNAc CPG variant (LK2506), with TEG as a spacer.

Reference

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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