CHAPTER 4: Antisense Technology: Liver Targeting and Beyond for Drug Discovery

Single-stranded phosphorothioate antisense oligonucleotides (ASOs) represent the most advanced RNA therapeutic technology today. The extensive characterization of the bio-distribution of systemically administered ASOs has established the hepatocyte as the most exploited cell type for antisense therapeutics to date for a broad range of human diseases. Beyond this initial cornerstone, further characterization of ASO subcellular trafficking has led to ligand–receptor targeting strategies and continued development of novel medicinal chemistries has supported the opportunity for ASO therapeutics across a broader range of tissue and cell compartments. Validation of novel routes of delivery has resulted also in the opening up of many new organ systems and cell types for human therapeutics.