A critical step in gene electrotransfer: the injection of the DNA

In gene electrotransfer, DNA must be injected before the electric pulses delivery. This is a critical step in the success of the gene transfer. Because plasmid molecule has a very high molecular weight, even large amounts of plamid (in mg) correspond to a few number of molecules that are highly diluted if injection is made intravenously. Therefore, injections are often made in the target tissue. We show the way in which that this intramuscular, intratumoral or intrahepatic injection is performed can largely impact on the result of gene transfer, even (and mainly) in the absence of electric pulses (1). Indeed, the simple injection of DNA into muscles is known to result in the expression of the injected genes, even though at low and variable levels. We report that this variability in DNA expression is partly dependent on the injection speed. The acceleration of the injection speed from values around 2 µl/s up to ones around 25 µl/s (depending on the tissue) results in a significant increase in gene expression in skeletal muscle (280 times on an average) and in liver (50 times) and a non-significant sevenfold increase in tumors.