Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase - increased expression with reduced muscle damage

The efficiency of plasmid gene transfer to skeletal muscle can be significa ntly improved by the application of an electrical field to the muscle follo wing injection of plasmid DNA. However, this electrotransfer is associated with significant muscle damage which may result in substantial loss of tran sfected muscle fibres. Reduction of the voltage used in the technique can r esult in a decrease in muscle damage, with a concomitant reduction in expre ssion, but without a significant decrease in the number of transfected fibr es. Pre-treatment of the muscle with a solution of bovine hyaluronidase gre atly increases the efficiency of plasmid gene transfer when used in conjunc tion with electrotransfer, but not when used alone. This combination treatm ent results in greatly enhanced levels of transfected muscle fibres without the increases in muscle damage associated with the electrotransfer process .