Gene delivery to the myocardium by intrapericardial injection

Several studies have demonstrated the feasibility of gene transfer into the heart muscle. However, ail the available data also indicate that the exten t of transfection remains limited As an alternative method to intravascular administration, we have developed a novel strategy which uses the pericard ial sac. When a replication-deficient adenovirus containing the cDNA encodi ng a bacterial beta-galactosidase is injected into the pericardial sac of a dult Wistar rats the staining is exclusively restricted to the pericardial cell layers. However, injecting a mixture of collagenase and hyaluronidase together with the virus, leads to a targe diffusion of the transgene activi ty reaching up to 40% of the myocardium. Transgene expression is predominan t in the left ventricle and the interventricular septum but limited in the right ventricle. In vivo echocardiographic measurements of the left ventric ular diameters at end diastolic and end systolic times show no difference b etween virus- and sham-injected animals, thus indicating a good clinical to lerance to this strategy of virus delivery The same protocol has been used with the same efficiency in mice, which leads us to propose injection into the pericardial sac as an effective and harmless method for gene transfer i nto the heart muscle.