Sustained expression of Fc-fusion cytokine following in vivo electroporation and mouse strain differences in expression levels

We previously demonstrated that cytokine expression following intramuscular gene transfer of a naked plasmid is increased 2 logs by in vivo electroporation, but the relatively low expression levels of the encoded protein is still A limitation for successful gene therapy and gene function studies. We recently reported that the serum viral IL-10 levels achieved by electroporation-mediated intramuscular delivery of pCAGGS-vIL10, a viral IL-10-expressing plasmid, can be further enhanced by modifying the plasmid into an immunoglobulin fusion protein expression plasmid, pCAGGS-vlL10/Fc. Here we examined the applicability of this approach to the expression of an endogenous cytokine, IL-10, in two different inbred mouse strains. We obtained sustained high serum levels of IL-10 in C3H/HeJ mice (C3H), but the level and duration of the gene expression was mouse-strain dependent. Although the serum IL-10 level was also increased by using the IL-10/Fc gene plasmid in C57BL/6 mice (B6), IL-10/Fc and a luciferase reporter showed significantly lower levels in B6 than in C3H mice, and the persistence of pCAGGS-IL10/Fc expression ranged from several days in B6 mice to more than one month in C3H mice. These results suggest that the electroporation-mediated intramuscular delivery of the immunoglobulin fusion protein expression plasmid is simple and very efficient, but mouse strain differences in transgene expression should be taken into consideration in its use.