*7.1. Self-Amplifying Systems for Both mRNA and DNA Vaccines*

Significant efforts have been expended to take advantage of a system employed by certain viruses, notably alpha viruses, which utilize a strategy of self-amplification of key viral proteins. Such self-amplifying replicon systems have been developed for viral vectors, plasmid DNA, and now mRNA [42–45]. These constructs encode viral proteins that result in the transduced cell producing many copies of mRNA encoding the protein of interest (i.e., the antigen) without making a whole viral particle. Thus, for a given DNA or mRNA vector, significantly more mRNA encoding the antigen and hence antigen protein, are made. In pre-clinical models, this has resulted in increased potency for these vectors on a per molecule of vector basis. The reason for the increased efficacy may be more than simply the increased amount of antigen produced, as the dsRNA intermediaries result in increased production of interferon and subsequently other immunologic effects, although the dsRNA can also have other possibly deleterious effects (see below).
