mRNA-Encoded antibodies as a next-generation therapeutic paradigm: a rapid and adaptive platform for the prevention and treatment of emerging and re-emerging infectious diseases - A critical review.

Messenger RNA (mRNA)-encoded antibodies represent a transformative therapeutic platform with the potential to rapidly combat emerging infectious diseases by enabling in situ expression of potent neutralizing antibodies directly in the patient's body. Unlike conventional monoclonal antibody (mAb) therapies, which rely on labor-intensive and time-consuming cell culture production, mRNA-encoded antibodies offer a faster, scalable, and cell-free approach that bypasses protein purification and cold-chain constraints. This strategy has demonstrated considerable promise during the COVID-19 pandemic, where Moderna's mRNA-1940, an mRNA-based neutralizing antibody targeting the SARS-CoV-2 spike protein, entered preclinical and early-phase trials within months of viral emergence, underscoring the potential for rapid response in outbreak settings. The platform leverages advances in nucleoside-modified mRNA, codon optimization, and lipid nanoparticle (LNP) delivery systems to achieve transient, high-level expression of functional antibodies with reduced innate immune activation. Beyond COVID-19, mRNA-encoded antibody approaches have been explored in preclinical models of Zika virus, Ebola virus, and rabies, where a single intramuscular dose provided prophylactic and therapeutic benefits in animal models. As the world faces recurrent viral threats, the development of mRNA-encoded antibodies as a plug-and-play system offers a compelling, adaptable, and clinically feasible strategy for infectious disease preparedness. This review explores the mechanistic foundation, delivery technologies, translational progress, case studies, safety considerations, and future clinical potential of mRNA-encoded antibodies in combating both pandemic and endemic infections.