What is, mutatis mutandis, the sequence of plasmid DNAs used in gene therapy?

Mutation is a fundamental biological process occurring in each living organism. Plasmid DNA which is used in gene therapy protocols or DNA vaccination passes through two different living cells which are, respectively, the producing cell (bacterial) and the target cell (eukaryotic). Hence, modifications in the nucleotide sequence of plasmids are likely to occur both in bacteria during the amplification step of plasmid DNA and in eukaryotic cells following gene transfer. In addition to these biological modifications resulting from the physical passage of the plasmid into two different living organisms, an additional source of sequence alteration resides in our mode of representation of the nucleotide sequence of plasmid DNA which uses a four letters code, whereas, bacterial DNA is made of six different nucleosides. Indeed, the therapeutic DNA paradigm seems to have neglected the qualitative importance of these DNA sequence alterations. In this review we discuss the importance and the role of these DNA sequence modifications in the context of non-viral gene therapy approaches.