AAPS 2026 PHARMSCI 360

Antibody–oligonucleotide conjugates (AOCs) represent an emerging class of targeted therapeutics that combine the cell‑specific delivery of monoclonal antibodies with the gene silencing or regulatory functions of oligonucleotides. By exploiting the antigen binding specificity of antibody, AOCs enable precise delivery of oligonucleotide payloads to tissues and cells that are difficult to reach with conventional oligonucleotide therapies, thereby expanding the therapeutic landscape to rare muscular diseases, cancers and central‑nervous‑system disorders. It is crucial to characterize the ADME properties of AOCs to optimize its distribution in target tissues and to understand its PK/PD properties. However, the complexity of AOCs structure presents significant challenges for bioanalysis. This presentation provides a systematic overview of integrated bioanalysis platform for AOCs. The workflow covers total antibody, conjugated AOC, free/total payload (siRNA/ASO), and OAR value using multiple platforms including LBA, LC-MS/MS, HRMS and qPCR, achieving a balance between sensitivity, specificity and throughput.