In vivo DNA electrotransfer into skeletal muscle and other tissues: mechanism and applications

The use of efficient procedures for DNA electrotransfer in various tissues such as the skin, liver, tumour and muscle is recent. Gene delivery to skel etal muscle is a promising strategy not only for the treatment of muscle di sorders but also for the systemic secretion of therapeutic proteins. Many p lasmid electrotransfer procedures have been proposed in the literature. One of the major well-known effects of the electric field on biological membra nes is their permeabilisation. However, contrary to the electropermeabilisa tion-induced uptake of small molecules into muscle fibres, plasmid DNA has to be present in the tissue during the electric pulses, suggesting a direct effect of the electric field on DNA during electrotransfer. The consistent ly additive effects of electropermeabilisation and DNA electrophoresis on e lectrotransfer efficiency were shown. Many applications of gene delivery to muscle are envisioned for the correction of myopathy, the local secretion of angiogenic or neurotrophic factors, and also for vaccination. Another ex citing application is the use of highly vascularised muscle as an endocrine organ for the systemic secretion of therapeutic proteins, such as erythrop oietin, alpha1-antitrypsin, clotting factors and anti-inflammatory cytokine s, etc. Experiments on the mouse model indicate that clinical applications can be anticipated. However, more work is need in order to assess the safet y profile of this technology, should it be applied to humans.