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.   

While the conjugation of N-acetylgalactosamine (GalNAc) residues has proven to be a clinically validated way of delivering therapeutic oligonucleotides to the liver, extrahepatic tissues delivery remains challenging. The conjugation of lipophilic moieties, such as cholesterol and fatty acids, has been shown to support the delivery of therapeutic oligonucleotides to non-liver tissues.  

 The conjugation of docosanoic acid (DCA) to oligonucleotides represents one of the earliest approaches to improve systemic delivery to cardiac and skeletal muscles and has been shown to induce a robust and prolonged gene silencing activity in these extrahepatic tissues, without causing any toxicities1. Our 3'-Docosanamino C7 CPG (LK2494) allows you to easily conjugate a DCA to the 3'-end of your oligonucleotides.  

1 Ref.: Biscans, A., Caiazzi, J., McHugh, N., Hariharan, V. N., Manish Muhuri, & Khvorova, A. (2021) Docosanoic acid conjugation to siRNA enables functional and safe delivery to skeletal and cardiac muscles. Molecular Therapy, 29(4), 1382–1394. https://doi.org/10.1016/j.ymthe.2020.12.023.