The success of an antibody-oligonucleotide conjugate rests as much on the targeting ligand as on the payload it carries. This blog walks through the four-step AOC mechanism, from receptor binding and internalisation through payload release and biological activity, and highlights endosomal escape as the field's most persistent bottleneck. It then sets out why VHHs are a strong fit for this role: their small size supports tissue penetration, their structural stability improves formulation robustness, their compact footprint gives access to sterically restricted epitopes, and their modular architecture allows tailored engineering for targeting and pharmacokinetics.
Link:
https://isogenica.com/why-vhhs-are-attractive-targeting-ligands-for-aocs/