Designing & Selecting Antibody-Oligonucleotide Conjugates (AOCs) for Enhanced Therapeutic Activity

Antibody-Oligonucleotide Conjugates (AOCs) hold real promise for expanding the therapeutic reach of oligonucleotides — but their complexity demands a systematic, multi-disciplinary approach to get the design right.

Our team recently shared a poster at the Oligonucleotides for CNS Summit Europe, exploring how our experts approach AOC development, covering some of the key decisions that shape a program:

– Antibody format: from full IgG to VHHs, format influences PK, tissue penetration, and delivery efficiency, with monovalent formats often preferred for CNS applications

– Oligonucleotide modification: finding the right 5′ or 3′ handle for linker coupling while preserving payload activity

– Bioconjugation strategy: comparing stochastic, site-specific, and ThioBridge® approaches to achieve controlled OAR 1 conjugates

– Lead screening: assessing internalization, gene knockdown, biophysical stability, & serum stability in parallel to identify the best candidates early

It’s a genuinely collaborative area to work in, and we’re proud of the expertise our team has built across each of these components. If you’re developing an AOC and want to discuss your program with our experts, we’d love to connect.

Download Poster 

Poster Authors :
Campbell Bunce, Nicolas Camper, Arron Hearn, Rob Holgate, Erika Kovacs, Johanna Midelet, Gabio Rossi, Gary Watts