Abstract
Gene therapy is emerging as a realistic addition to the therapeutic arsenal in heart failure, but the search for suitable vectors for cardiac transfection is still ongoing. In this study, we explore the applicability of recombinant Semliki Forest virus (SFV) in heart failure. SFV was intracoronarily delivered 2 weeks after induction of myocardial infarction in the rat model for heart failure. Duration of SFV expression was determined, and tissue distribution was studied by histochemical, biochemical, and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Expression of SFV-mediated transfection in the heart reached its maximum after 48–72 h and subsided within a week. Intracoronary administration of SFV efficiently transfected the non-infarcted cardiac wall, resulting in high levels of β-galactosidase (β-gal) activity (1337 ± 537 IU/mg) and lacZ RNA in the hearts of all rats, whereas brain, kidney, liver, lung, spleen, and testis were lac Z negative. In conclusion, intracoronarily delivered SFV has a favourable distribution pattern, showing expression of the transgene restricted to the heart.
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