Catheter-delivered in vivo gene transfer into rat myocardium using the fusigenic liposomal mediated method

We compared the efficacy of four different in vivo hemagglutinating virus of Japan (HVJ)-liposome gene transfer methods, i.e, direct myocardial rejection (IM), injection into the left ventricular cavity (LV), infusion at the level of the coronary cusps (CI), or injection into the left ventricular cavity with a balloon catheter blocking aortic flow (LV+B) to transfer β-galactosidase, FITC-labeled oligodeoxynucleotide (ODN), and/or luciferase genes into the rat heart. IM caused highly efficient gene transfer in the limited area around the rejection site, which suggests that IM may be a statable method for targeted treatment of focal lesion. In the LV+B group, all rats had myocardial β - galactosidase staining and fluorescence of FITC-labeled ODN in the nuclei of cardiac myocytes around the coronary arteries and the vasa vasorum, and some transfected myocytes were observed in the middle of the myocardium without any evidence of injury. In contrast, in the CI group, only half of the animals had myocardial expression of β - galactosidase. In contrast, fluorescence or luciferase activity was present throughout the left ventricle in the LV+B group. However, the percentage of myocytes that exhibited fluorescence was less than 1% of the total ventricular myocyte population and luciferase activity in the LV+B group was 1 6% of that in the IM group. No evidence of luciferase expression was observed in brain, lung, liver, kidney, or testis in either the IM or LV+B group. These results suggest that HVJ-liposome gene transfer into the myocardium through the coronary arteries using a balloon-catheter technique is safe and has the potential for causing widespread transgene expression with organ-specificity, although the efficiency of gene transfer should be improved.