BETA-GALACTOSIDASE STAINING FOLLOWING INTRACORONARY INFUSION OF CATIONIC LIPOSOMES IN THE IN-VIVO RABBIT HEART IS PRODUCED BY MICROINFARCTION RATHER THAN EFFECTIVE GENE-TRANSFER - A CAUTIONARY TALE

The myocardium is a potential target for the expression of exogenous g enes to treat inherited and acquired diseases. Although adenovirus-med iated gene transfer has resulted in high-level gene transfer in vivo v ia direct intramyocardial injection and via a percutaneous intra-arter ial route, the time-course of gene expression is limited by host immun e responses. It was the aim of this study to test whether cationic lip osome-mediated gene transfer, which does not suffer from the aforement ioned problems, was feasible in the adult rabbit myocardium via a perc utaneous transluminal approach. Doses of plasmid DNA encoding lacZ fro m 200-800 mu g complexed to cationic liposomes resulted in X-gal conve rsion at day 3 with associated myocardial damage. We hypothesised that the damage was associated with macro-aggregates of cationic liposomes -DNA occluding the microcirculation. When such aggregates were exclude d no X-gal conversion was seen in vivo. In order to show that X-gal co nversion occurs in areas of infarction in the myocardium we caused clo sed chest infarction by deploying a plantinum micro-embolisation coil in the circumflex coronary artery. At day 3 X-gal conversion was obser ved in the territory supplied by the occluded artery. Thus, microinfus ion causes the false positive appearance of gene transfer when using a lacZ reporter gene.