Application of nucleic acid-encoded antibodies in prevention and treatment of emerging viral infectious diseases

Abstract

<p indent="0mm">Emerging viral infectious diseases are diverse, fast-spreading and dangerous and have caused many outbreaks and epidemics worldwide, with serious and far-reaching effects on human health, social stability and economic development. At present, vaccines, small-molecule drugs and monoclonal antibodies (mAbs) are important tools for addressing new outbreaks of viral infectious diseases and have played key roles in the prevention and treatment of multiple viral infectious diseases. In particular, mAbs can effectively prevent a virus from entering host cells and block reinfection by progeny virus. mAbs can also facilitate the clearance of viruses and virus-infected cells via Fc-mediated effector functions. In addition, the effects of mAbs are related to several characteristics, such as their high specificity, ability to enhance immune responses and low toxicity. Thus, mAbs are appealing as potential therapeutics and prophylactics for viral infections. However, traditional mAb technology still has some limitations, such as complex production processes, high quality control requirements, high manufacturing costs, high treatment costs, and the need for strict cold chain storage and transportation, making it unsuitable for large-scale population use. Unfortunately, to date, only a small number of mAb drugs have been used to treat or prevent infectious diseases. Therefore, there is a need to rapidly develop a novel antiviral tool. As a type of novel biological agent, nucleic acid-encoded antibodies are DNA and mRNA molecules that encode virus-specific neutralizing antibodies that are appropriately sequenced and optimally regulated to obtain stably expressed DNA and mRNA molecules <italic>in vitro</italic>, which are then introduced into a host through a special delivery vehicle. Then, the host cells are used as individual bioreactors, and the protein synthesis mechanism is used to express structurally and functionally intact antibodies, which in turn act as neutralizing agents <italic>in vivo</italic>. Compared to traditional mAbs, nucleic acid-encoded antibodies have many potential advantages, such as ease and speed of design and testing, ease of rapid scale-up and manufacturing, ease of storage and transportation, and cost-effectiveness; consequently, they are considered an ideal alternative to traditional mAb technology. At present, nucleic acid-encoded antibodies have been used in preclinical studies on diseases caused by many viruses, such as human immunodeficiency virus, influenza virus, Chikungunya virus, Zika virus and SARS-CoV-2. Specifically, three nucleic acid-encoded antibodies have entered phase I clinical trials and have promising applications in the prevention and treatment of emerging viral infectious diseases. In this paper, we summarize the principles and current research status of nucleic acid-encoded antibodies in antiviral control and highlight the advantages of nucleic acid-encoded antibodies over traditional protein antibodies, the advantages and disadvantages of different nucleic acid-encoded antibodies, and the potential challenges and possible strategies for the future development of these agents to provide new research ideas for the application of nucleic acid-encoded antibodies in the control of future emerging viral infectious diseases.