Overcoming Limitations and Advancing the Therapeutic Potential of Antibody-Oligonucleotide Conjugates (AOCs): Current Status and Future Perspectives

As cancer incidence rises due to an aging population, the importance of precision medicine continues to grow. Antibody-drug conjugates (ADCs) exemplify targeted therapies by delivering cytotoxic agents to specific antigens. Building on this concept, researchers have developed antibody-oligonucleotide conjugates (AOCs), which combine antibodies with oligonucleotides to regulate gene expression. This review highlights the mechanism of AOCs, emphasizing their unique ability to selectively target and modulate disease-causing proteins. It also explores the components of AOCs and their application in tumor therapy while addressing key challenges such as manufacturing complexities, endosomal escape, and immune response. The article underscores the significance of AOCs in precision oncology and discusses future directions, highlighting their potential in treating cancers driven by genetic mutations and abnormal protein expression.