Abstract
Nucleic acid-based medicines such as small interfering RNA（siRNA） and antisense oligonucleotides（ASOs） have great potential to address undruggable targets that use classical small-molecule approaches or traditional biologics. GalNAc-ligand-conjugated oligonucleotides, which targets the asialoglycoprotein receptor（ASGPR） on hepatocytes, is the most validated for targeted delivery of oligonucleotides, have been under evaluation in clinical trials for modulation of various liver-disease-related genes and includes several FDA-approved drugs. Given the success of GalNAc–oligonucleotides, ligand-conjugated oligonucleotides outside the liver are expected to create the novel drugs. However, receptor-mediated targeted delivery outside the liver using ligand-conjugated oligonucleotides remains challenging. We have investigated targeted delivery of siRNA to extrahepatic tissues/cells using glycan conjugated siRNA because we focused on unique binding properties between ligand and receptor result in enhancement of uptake amount of payloads into the cells. In this paper, we introduce a case study.
