**1. Introduction**

Plasmid DNA [1] and now mRNA [2] vaccines have generated significant interest and efforts because of their potential as platform technologies that could be used for a variety of applications ranging from prophylaxis to therapy and from personalized medicine to global health solutions. Both can be quickly made with fairly generic manufacturing processes and can be constructed directly from the genetic sequence of the desired protein, whether the origin of the protein is human or from a pathogen. For vaccines, making a gene construct coding for the antigen instead of inactivating or attenuating the pathogen, or instead of making a recombinant protein, is vastly easier, more rapid, and avoids potential risks of working with live pathogens. Likewise, the vaccine construct can encode only the key antigen without including other proteins that may be either deleterious (such as toxins) or that may be irrelevant for protection yet immunodominant.

The ease and speed of making the constructs also means that these are considered potential gamechangers for targeting epidemic or emerging diseases where rapidly designing, constructing, and manufacturing the vaccine are crucial. For cancer, rather than relying on tumor-associated antigens that are common to many tumors, it would require little more effort to make the vaccines specific for that individual's exact tumor antigens, now referred to as personalized vaccines. The concept was demonstrated pre-clinically in the mid-1990s with DNA vaccines targeting lymphoma, where the idiotype of a tumor could be rapidly sequenced, and a DNA vaccine made much more quickly than a recombinant protein version [3,4]. Alternatively, as is being tested now for mRNA [2,5], libraries of gene-based constructs encoding various antigens could be made. Then, based on a patient's individual tumor antigens, a combination of constructs could be easily combined from this pre-made library.

At a time when many scientists are turning from plasmid DNA to explore mRNA technology while remaining uncertain about when or whether DNA vaccines will be licensed for human diseases, it is useful to compare the two technologies by analyzing both the theoretical issues and the experimental data and progress for both.
