Beyond the liver: how conjugation is advancing delivery for oligonucleotide therapeutics

Oligonucleotide therapeutics have delivered on their promise in the liver, where a fenestrated endothelium and abundant hepatocyte receptors do much of the work. Most of the disease landscape, however, lies beyond it, and conjugation is becoming the central strategy for getting there. In the first cross-journal collaboration between Nucleic Acid Insights and Bioconjugate Insights, a panel of leading experts examines how conjugation is extending oligonucleotide delivery into muscle, the central nervous system, the lung, and the kidney. The discussion covers linker design and payload loading, the characterization demands created by hybrid chemistries, the manufacturing requirements that separate a platform from a one-off success, and what would signal that the field has genuinely moved beyond the liver.