Label-free quantification of antibody–oligonucleotide conjugates with varying stoichiometries using capillary zone electrophoresis

We report a label-free capillary zone electrophoresis platform enabling quantitative analysis of antibody-oligonucleotide conjugate (AOC) heterogeneity with single-stranded oligonucleotide (21 nt) resolution. This methodology resolves free antibodies, oligonucleotides, and AOC subpopulations while precisely evaluating conjugation efficiency and oligonucleotide-to-antibody ratio (OAR) heterogeneity across three synthetic strategies.