Oligonucleotide therapeutics are single-stranded synthetic oligonucleotides and often show modifications in their structure to improve PK properties and stability. They generally target RNA transcripts and reduce or modify the corresponding protein expression. For example, Anti-sense oligonucleotides (ASO) are complementary to a specific mRNA that can impede the expression of a gene e.g., by inhibiting transcription and translation of the corresponding protein. Unlike monoclonal antibodies, the oligonucleotides are relatively small with fewer epitopes and are delivered to immune restricted sites to remain locally confined. Moreover, they can trigger an immune response and are able to elicit the formation of anti-drug antibodies (ADAs). Therefore, regulatory agencies require the testing of immunogenicity and reporting of the data as part of new drug applications. This necessitates highly specific and sensitive antibodies for the development of an assay to detect ADAs in patient samples.

Crucial to the development of these bioanalytical assays are antibody reagents that specifically recognize modified oligonucleotides. However, generating modified oligonucleotide-specific antibodies is not a trivial task, as it presents challenges such as poor antigen immunogenicity and the need to differentiate between the modified therapeutic molecules and endogenous counterparts.