The high selectivity and affinity of antibodies toward their antigens have made them a highly valuable tool in disease therapy, diagnosis, and basic research. A plethora of chemical and genetic approaches have been devised to make antibodies accessible to more “undruggable” targets and equipped with new functions of illustrating or regulating biological processes more precisely. In this Review, in addition to introducing how naked antibodies and various antibody conjugates (such as antibody-drug conjugates, antibody-oligonucleotide conjugates, antibody-enzyme conjugates, etc.) work in therapeutic applications, special attention has been paid to how chemistry tools have helped to optimize the therapeutic outcome (i.e., with enhanced efficacy and reduced side effects) or facilitate the multifunctionalization of antibodies, with a focus on emerging fields such as targeted protein degradation, real-time live-cell imaging, catalytic labeling or decaging with spatiotemporal control as well as the engagement of antibodies inside cells. With advances in modern chemistry and biotechnology, well-designed antibodies and their derivatives via size miniaturization or multifunctionalization together with efficient delivery systems have emerged, which have gradually improved our understanding of important biological processes and paved the way to pursue novel targets for potential treatments of various diseases.

中文翻译：

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新时代的黎明：以抗体为基础的疗法瞄准“不可成药”

抗体对其抗原的高选择性和亲和力使其成为疾病治疗、诊断和基础研究中非常有价值的工具。人们设计了大量的化学和遗传方法，使抗体能够接触到更多“不可成药”的靶标，并配备更精确地说明或调节生物过程的新功能。在这篇综述中，除了介绍裸抗体和各种抗体偶联物（例如抗体-药物偶联物、抗体-寡核苷酸偶联物、抗体-酶偶联物等）如何在治疗应用中发挥作用外，还特别关注了化学工具如何发挥作用有助于优化治疗结果（即增强疗效并减少副作用）或促进抗体的多功能化，重点关注新兴领域，如靶向蛋白质降解、实时活细胞成像、催化标记或时空控制的脱壳以及细胞内抗体的参与。随着现代化学和生物技术的进步，通过尺寸小型化或多功能化以及高效的递送系统精心设计的抗体及其衍生物已经出现，这逐渐提高了我们对重要生物过程的理解，并为寻找潜在治疗的新靶点铺平了道路。各种疾病。