Oligonucleotide therapeutics have the potential to treat a myriad of different diseases, however, their efficient delivery to targeted cells and organs remains challenging. Their high molecular size and anionic backbone hinder their cellular uptake. In addition, unmodified oligonucleotides are prone to endonuclease degradation, rapid elimination from the systemic circulation, and can trigger an immune response. Various delivery technologies have been developed to improve oligonucleotide cell delivery, including viral and non-viral carriers, and direct conjugation of oligonucleotides to ligand moieties, such as lipids.

While the conjugation of N-acetylgalactosamine (GalNAc) residues has proven to be a clinically validated way of delivering therapeutic oligonucleotides to the liver, extrahepatic tissue delivery remains challenging. The conjugation of long-chain fatty acids and their derivatives, such as lauric acid (C12), palmitic acid (C16), stearic acid (C18) and docosanoic acid (C22) have been shown to support the delivery of therapeutic oligonucleotides to non-liver tissues.

[Ref.: Annabelle Biscans, Andrew Coles, Reka Haraszti, Dimas Echeverria, Matthew Hassler, Maire Osborn, Anastasia Khvorova, Diverse lipid conjugates for functional extra-hepatic siRNA delivery in vivo, Nucleic Acids Research, Volume 47, Issue 3, 20 February 2019, Pages 1082–1096, https://doi.org/10.1093/nar/gky1239]

Lauric acid (systematically dodecanoic acid) is a saturated fatty acid with a 12-carbon atom chain. It is a component of triglycerides and is found, among other things, in coconut milk, palm kernel oil, and human breast milk. It is mainly used in the composition of soaps and cosmetics.

Our 3'-Dodecanamido-C7 CPG (BG8-1004) and Dodecanamido-C7 CE-Phosphoramidite (LK2505) allow you to easily conjugate a dodecanoic acid chain to your oligonucleotides.