The Dawn of a New Era: Targeting the Undruggables with Antibody-Based Therapeutics

The high selectivity and affinity of antibodies towardtheir antigenshave made them a highly valuable tool in disease therapy, diagnosis,and basic research. A plethora of chemical and genetic approacheshave been devised to make antibodies accessible to more undruggabletargets and equipped with new functions of illustrating or regulatingbiological processes more precisely. In this Review, in addition tointroducing how naked antibodies and various antibody conjugates (suchas antibody-drug conjugates, antibody-oligonucleotide conjugates,antibody-enzyme conjugates, etc.) work in therapeutic applications,special attention has been paid to how chemistry tools have helpedto optimize the therapeutic outcome (i.e., with enhanced efficacyand reduced side effects) or facilitate the multifunctionalizationof antibodies, with a focus on emerging fields such as targeted proteindegradation, real-time live-cell imaging, catalytic labeling or decagingwith spatiotemporal control as well as the engagement of antibodiesinside cells. With advances in modern chemistry and biotechnology,well-designed antibodies and their derivatives via size miniaturizationor multifunctionalization together with efficient delivery systemshave emerged, which have gradually improved our understanding of importantbiological processes and paved the way to pursue novel targets forpotential treatments of various diseases.

Automated summary

The high selectivity and affinity of antibodies have made them valuable tools in disease therapy, diagnosis, and basic research. Various chemical and genetic approaches have been developed to improve their effectiveness and expand their applications in areas such as targeted protein degradation, real-time live-cell imaging, and catalytic labeling or decaging. Advancements in chemistry and biotechnology have led to well-designed antibodies and their derivatives that improve our understanding of biological processes and offer potential treatments for various diseases.