Better Linker Chemistry Lifts siRNA Antibody-Conjugate Delivery
- A new bioRxiv preprint investigates how the chemical architecture of antibody-oligonucleotide conjugates (AOCs) affects their performance as siRNA delivery vehicles.
- The work examines design variables such as linker composition, conjugation site on the antibody, and siRNA chemical modification pattern.
- Findings aim to clarify which structural choices most influence knockdown potency and delivery efficiency, informing rational AOC design.
💡 Points
Whether AOC chemists can transplant ADC lessons on conjugation-site control and linker stability wholesale — or oligo payloads demand their own rules — matters more than the siRNA payload itself. Locking down DAR and site-specificity is what turns AOCs into the extrahepatic answer GalNAc conjugates can't be, which is exactly why Alnylam, Avidity, and everyone else is racing to nail this chemistry first.
Enhancing the efficacy of siRNA Antibody Oligonucleotide Conjugates (AOCs) through chemical design ↗