A directed approach to the delivery of therapeutic oligonucleotides specifically to the liver has been to target the asialoglycoprotein receptor (ASGPR) using a suitable glycoconjugate. Indeed, ASGPR is the ideal target for delivery of therapeutic oligonucleotides to the liver since it combines tissue specificity, high expression levels and rapid internalization and turnover. The use of oligonucleotide glycoconjugates has led to significant advances in therapeutic delivery as evidenced by the work of Alnylam Pharmaceuticals and Ionis Pharmaceuticals using multivalent N-acetylgalactosamine (GalNAc) oligonucleotide conjugates.
Glen Research is delighted to introduce a GalNAc modification strategy using a monomeric GalNAc support and the equivalent GalNAc phosphoramidite. Our experimental work has shown that these products are fully compatible with regular oligonucleotide synthesis and deprotection. Oligonucleotides containing GalNAc can be deprotected using standard procedures during which the acetyl protecting groups on GalNAc are removed. We have demonstrated that 5’-GalNAc C3 phosphoramidite can be used to prepare oligonucleotides with multiple consecutive GalNAc additions at the 5’ terminus.
Glen Research offers these GalNAc C3 products under an agreement with AM Chemicals LLC.Â
(4-(Trimethoxytrityloxymethyl)-1-(6-(4-(3,4,6-O-triacetyl-2-acetylamino-2-deoxy-β-D-galactopyranosyl)butanamido)hexanoyl)piperidin-4-yl)methyl-O-[(2-cyanoethyl)-(N,N-diisopropyl)] phosphoramidite
(4-(Trimethoxytrityloxymethyl)-1-(6-(4-(3,4,6-O-triacetyl-2-acetylamino-2-deoxy-β-D-galactopyranosyl)butanamido)hexanoyl)piperidin-4-yl)methyl-O-succinoyl CPG