Potential therapeutic oligonucleotides must permeate the cell membrane for optimal activity. The addition of lipophilic groups to an oligonucleotide would be expected to enhance cellular uptake/membrane permeation. The use of cholesteryl oligos and the consequent improvement in activity has been described. We have designed our Cholesteryl products with triethyleneglycol (TEG) spacers for maximum solubility. Vitamin E is both lipophilic and non-toxic even at high doses so would be an excellent candidate as a lipophilic carrier for oligonucleotides. Therefore, as an addition to our cholesteryl product line, we offer simple ?-tocopheryl (vitamin E) labelling. Totally synthetic ?-tocopherol is racemic at its three chiral centers and is used to prepare this product. The 5'-stearyl group may also become a favored lipophilic carrier for experimentation with synthetic oligonucleotides. 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.