The research progress on the design and application of mRNA antibody technology

With the rapid advancement of mRNA technology, particularly driven by the unprecedented success of mRNA vaccines against COVID-19, strategies have gained significant importance in both the prophylaxis and treatment of diseases, emerging as a transformative force in modern biopharmaceutical innovation. This technological breakthrough has not only overcome traditional bottlenecks in biopharmaceutical development but also accelerated research and industrialization in multiple fields, including the neutralizing antibody drugs for infectious diseases, protein replacement therapies for rare genetic disorders, and novel tumor immunotherapies. Consequently, mRNA-encoded antibody technology has become one of the most prominent and rapidly evolving research directions in the global biopharmaceutical landscape. mRNA-encoded antibody technology involves in vitro transcription and synthesis of mRNA encoding full-length antibodies (monoclonal/bispecific), antibody fragments (Fab/scFv), or antibody-drug conjugates (ADCs). These mRNA constructs are then precisely delivered into host cells via lipid nanoparticles (LNPs) to overcome the inherent instability of naked mRNA and enable efficient intracellular uptake. Once internalized, the delivered mRNA utilizes the host cell’s endogenous ribosomal translation machinery to produce the target antibody, which is subsequently secreted into the extracellular milieu to exert biological effects.Compared with conventional protein-based antibodies, mRNA-encoded antibodies possess several unique technical characteristics and advantages. First, the mRNA-encoded antibody platform entirely eliminates reliance on complex cell culture or bacterial fermentation systems. Efficient mRNA synthesis is achieved through standardized in vitro transcription reactions, significantly streamlining production workflows and reducing dependence on specialized manufacturing facilities. Beyond manufacturing innovations, following the acquisition of heavy and light chain gene sequences, mRNA-encoded antibodies can be prepared and undergo preliminary validation as candidate therapeutics within an exceptionally short timeframe. This characteristic confers unparalleled strategic value in countering rapidly mutating pathogens. Additionally, the establishment of standardized production platforms enables the application of identical technical workflows to antibody products targeting different antigens, achieving significant economies of scale and cost benefits. Ultimately, the high degree of standardization in mRNA synthesis and purification technologies ensures consistent and reproducible product quality, facilitating the implementation of unified quality control standards. Collectively, these advantages establish a robust foundation for the application of mRNA-encoded antibodies in multiple fields.In this review, we systematically elucidate the fundamental principles of mRNA-encoded antibody technology, including the design of optimal mRNA constructs and the development of advanced delivery systems. We also comprehensively explore key chemical modification strategies that enhance mRNA stability, reduce immunogenicity, and improve translation efficiency. Furthermore, we summarize the recent progress in the application of different mRNA-encoded antibody types in viral infectious diseases, tumors, and immune-mediated disorders, highlighting landmark preclinical and clinical studies. Finally, we discuss the current challenges hindering the clinical translation of mRNA-encoded antibodies and propose corresponding future optimization strategies, such as tissue-specific delivery systems and innovative administration routes. Collectively, this review aims to provide a comprehensive and up-to-date theoretical reference for researchers in the field, facilitating the further optimization and clinical application of mRNA-encoded antibody platforms.