Antibody Modification via Lipoic Acid Ligase A‐Mediated Site‐Specific Labeling

Abstract Enzymatic modification, particularly utilizing lipoic acid ligase (LplA), has emerged as a transformative approach in biopharmaceuticals, enabling precise and site‐specific protein modifications. This review delves into the innovative applications of LplA in antibody modifications, including the creation of antibody‐drug conjugates (ADCs) and the advancement of tag‐free conjugation techniques. LplA's ability to facilitate the incorporation of bioorthogonal groups and its adaptability to various substrates underscores its versatility. Key developments include the successful generation of dual‐labeled antibodies and the application of LplA in modifying antibody fragments. Additionally, the review explores the potential for LplA to enhance the therapeutic efficacy of ADCs through improved drug‐to‐antibody ratios and site‐specific payload attachment. The implications of these advancements are significant, suggesting that LplA‐mediated modifications could lead to more effective and targeted antibody‐based therapies. This review aims to provide a comprehensive overview of LplA's role in expanding the possibilities of enzymatic conjugation, setting the stage for future research and clinical applications.