EFFICIENT GENE-TRANSFER INTO MYOCARDIUM BY DIRECT-INJECTION OF ADENOVIRUS VECTORS

Previous studies have established that gene transfer into myocardial c ells in vivo is detectable after direct injection of plasmid DNA. Rece ntly, adenovirus vectors have been shown to provide an efficient metho d for gene transfer into a wide range of tissues. Therefore, this stud y sought to assess the efficiency and stability of adenovirus-mediated gene transfer into myocardium and to compare this method with that us ing plasmid-based gene transfer techniques. Adult rats underwent myoca rdial injection via a subdiaphragmatic approach. Gene transfer efficie ncy was compared using direct injection of an adenovirus vector encodi ng for the marker gene beta-galactosidase (beta-gal), a control adenov irus vector encoding for the cystic fibrosis transmembrane conductance regulator gene, a plasmid encoding for beta-gal, or a control plasmid . Hearts infected with an adenovirus vector containing the beta-gal ge ne showed significantly increased beta-gal enzymatic activity compared with hearts injected with beta-gal plasmid. Histological examination revealed that cardiac myocytes were the target of adenovirus-mediated gene transfer. A time course of gene expression showed that beta-gal e nzymatic activity peaked during the first week following injection. Ad enovirus vectors provide an efficient but transient method for in vivo gene expression in myocardium.