A comparison of efficacy and toxicity between electroporation and adenoviral gene transfer

Intra-muscular DNA transfer of pLuciferase was increased by 2 logs after electroporation, confirming data described by others. However, the blood levels of the encoded protein were still lower than those obtained after injection of first generation adenoviral vectors. Also, the electroporation procedure, on its own, caused severe muscle damage consisting of rhabdomyolysis and infiltration, whereas the adenoviral vectors caused only a slight infiltration. As damage of targeted tissue may be an advantage in the case of tumour transfection, we also compared the two transfection methods in tumour tissue. In case of poorly permissive tumours, adenoviral vectors cannot transfect more than 2% of the tumour tissue without inducing significant liver damage. In contrast, the electroporation seems to offer a wider therapeutic window since it does not cause any systemic toxicity and still induce's significant transfection.Plasmid electroporation of the muscle induce severe local damage and is of no advantage over adenoviral vectors for obtaining high blood levels of a vector encoded protein. In contrast, electroporation of tumours might be safer than adenoviral gene transfer.Numerous diseases require treatment by systemic delivery of a therapeutic protein. Repetitive or continuous injections are the only delivery method used in daily practice. As a mean of reducing the inconvenience of multiple injections or implantation of mini pumps, gene transfer technology may offer certain advantages. In order to achieve a high plasma concentration, whatever the vector used, the transfection of a large tissue mass is required (e.g. liver or muscle). In rodents, intravenous injection of a non-targeted vector – viruses or plasmid preparations – induces mainly transfection in the liver and the spleen [1,2]. As of today, transfection of other large organs by viral vectors has not been accomplished in by way of systemic delivery [3]. The main inconveniences of intravenous administration of firs