Advances in the pharmaceutical development of antibody-oligonucleotide conjugates

Antibody-oligonucleotide conjugates (AOCs) are a novel class of therapeutics composed of an antibody, a linker, and an oligonucleotide. AOCs combine the antigen-specific binding capability of an antibody and the gene-regulatory function of an oligonucleotide to achieve targeted and efficient therapeutic intervention across a range of diseases. Although AOCs are in the early stages of development, progress has been steady over the last few decades. The structural complexity and mechanistic diversity of AOCs contribute to manufacturing and quality control challenges, requiring strategies to ensure therapeutic efficacy and minimize off-target toxicity. The design, manufacturing, and quality control of AOCs are essential to ensuring their safety and efficacy. This review summarizes the history and current clinical development of AOCs, focusing on mechanisms of action, molecular design with various linkers, and recent advances in manufacturing processes and quality control. Additionally, the current challenges and future prospects for the development of AOC therapeutics are highlighted.