A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Liu, Margaret A.

The same 1990 publication also demonstrated that naked RNA could similarly result in the in vivo expression of encoded protein. However, more attention focused on utilizing plasmid DNA, rather than mRNA, likely because of concerns about the instability of mRNA. In 1992, Bloom and colleagues [8] demonstrated the efficacy of mRNA to express protein in vivo by showing that mRNA encoding a hormone could correct a disease following direct injection into rat brains. In the same year (1993) that the first demonstration of the ability of DNA plasmid to protect mice from heterosubtypic challenge with influenza was published [7] , liposome-formulated mRNA was also shown to generate influenza-specific cytolytic T cells in mice [9] (although protection from infectious challenge, as was shown for plasmid DNA, was not tested, perhaps explaining part of the difference in excitement about the technologies). Nevertheless, for both entities, a key issue was how to optimally deliver the DNA plasmid or the mRNA into the desired cells, either for optimal expression of the desired therapeutic protein as a drug or for gene therapy (to supply a missing or defective protein), or to generate the desired immune response against the protein if it were an antigen. For gene therapy, the encoded protein needs to not stimulate an immune response. For a vaccine, which cell produces the protein encoded by the mRNA or the plasmid DNA can be a key issue because, although for antibodies [10] where the protein would likely need to be secreted, for cellular immune responses of the Cytolytic T Lymphocyte variety [11] , the type of cell producing the protein (and hence the cell type transduced by the plasmid DNA or the mRNA) is relevant, as is discussed later.