Vaccination with Messenger RNA: A Promising Alternative to DNA Vaccination

The first proof-of-concept studies about the feasibility of genetic vaccines were published over three decades ago, opening the way for future development. The idea of nonviral antigen delivery had multiple advantages over the traditional live or inactivated pathogen-based vaccines, but a great deal of effort had to be invested to turn the idea of genetic vaccination into reality. Although early proof-of-concept studies were groundbreaking, they also showed that numerous aspects of genetic vaccines needed to be improved. Until the early 2000s, the vast majority of effort was invested into the development of DNA vaccines due to the potential issues of instability and low in vivo translatability of messenger RNA (mRNA). In recent years, numerous studies have demonstrated the outstanding abilities of mRNA to elicit potent immune responses against infectious pathogens and different types of cancer, making it a viable platform for vaccine development. Multiple mRNA vaccine platforms have been developed and evaluated in small and large animals and humans and the results seem to be promising. RNA-based vaccines have important advantages over other vaccine approaches including outstanding efficacy, safety, and the potential for rapid, inexpensive, and scalable production. There is a substantial investment by new mRNA companies into the development of mRNA therapeutics, particularly vaccines, increasing the number of basic and translational research publications and human clinical trials underway. This review gives a broad overview about genetic vaccines and mainly focuses on the past and present of mRNA vaccines along with the future directions to bring this potent vaccine platform closer to therapeutic use.