Post-translational assembly of multi-functional antibody

The advent of multi-specific antibodies has introduced a significant advantage over traditional monoclonal antibody therapeutics by engaging multiple targets and pathways. This review delves into the post-translational assembly techniques for multi-specific antibodies, highlighting the innovations and challenges associated with approaches of chemical conjugation, oligonucleotide-mediated assembly, and protein-protein interactions. Chemical conjugation methods have evolved to enhance the assembly process's specificity and flexibility, enabling transient engagement and versatile antibody formats. Meanwhile, oligonucleotide-mediated assembly leverages the precision of Watson–Crick base pairing, granting unmatched control over the antibody's structure and functional orientation. Additionally, protein-protein interaction strategies, notably through SpyTag/SpyCatcher systems, present a direct assembly approach without necessitating ancillary modifications, streamlining the production process. This review summarizes the significance of these methodologies in generating antibodies with diverse structures and multi-target engagement capabilities, underscoring their potential in improving therapeutic efficacy and reducing production complexity.