No abstract

Long-term high-level in vivo gene expression appears to depend on the promoter chosen to drive the gene of choice. In many cases the promoter appears to 'switch off some time after in vivo gene transfer. We demonstrate that, following intramuscular injection of ß-galactosidase reporter plasmids, promoter 'switch off is due to elimination of fibres expressing the transferred reporter gene by activation of a Thl (cytotoxic) immune response. This finding, in the absence of stimulation of the immune system by viral vector proteins, has implications not only for gene transfer experiments but for the future of muscledirected gene therapy.

The use of antisense oligonucleotides (AOs) to induce exon skipping leading to generation of an in-frame dystrophin protein product could be of bene¢t in around 70% of Duchenne muscular dystrophy patients. We describe the use of hyaluronidase enhanced electrotransfer to deliver uncomplexed 2P P-Omethyl modi¢ed phosphorothioate AO to adult dystrophic mouse muscle, resulting in dystrophin expression in 20^30% of ¢bres in tibialis anterior muscle after a single injection. Although expression was transient, many of the corrected ¢bres initially showed levels of dystrophin expression well above the 20% of endogenous previously shown to be necessary for phenotypic correction of the dystrophic phenotype.

Background: Consumption of a mixed meal increases postprandial carbohydrate utilization and decreases fat oxidation. On the other hand, acute endurance exercise increases fat oxidation and decreases carbohydrate utilization during the post-exercise recovery period. It is possible that the resulting post-exercise increase in circulating nonesterified fatty acids could attenuate the ability of ingested carbohydrate to inhibit lipid oxidation. The purpose of this study was to determine whether prior exercise attenuates the usual meal-induced decline in lipid oxidation.