There are a few chemical approaches or methods for linking antibodies to ASOs. These are:
Click chemistry utilizes azide-alkyne cycloaddition reactions, enabling bioorthogonal site-specific conjugation.
Disulfide linker chemistry allows the generation of cleavable conjugates in reducing environments. These conjugates enable the release of ASO in the intracellular space.
Hydrazone or oxime ligation utilizes aldehyde-modified oligonucleotides with hydrazine-functionalized antibodies.
Thiol-maleimide chemistry introduces thiol groups on either the ASO or antibody for the reaction with maleimide-modified target molecules. This approach is efficient and widely used.