Antibody-Oligonucleotide Conjugates (AOCs) Development

Oligonucleotides, as drug molecules, suffer from several drawbacks such as instability, impaired pharmacokinetics (PK), poor cellular uptake and sub-optimal tissue targeting. Chemical modification of oligonucleotides is therefore frequently required to transform a base sequence into a viable medicine. Backbone modifications impart enhanced stability and PEGylation has been employed to improve PK properties. Tissue-specific delivery of oligonucleotides can be facilitated via conjugation to a targeting moiety (e.g. a monoclonal antibody or mAb for short). A wide array of heterobifunctional linkers exist which can be utilized for oligonucleotide bioconjugation. Oligonucleotides functionalized with 3’ or 5’-terminal amine, thiol or click chemistry groups facilitate conjugation to PEG or a targeting protein.