In vivo transfer efficiency of antisense oligonucleotides into the myocardium using HVJ-liposome method

Although antisense strategy has been at the center of interest in gene therapy, little is known about application of this strategy to cardiac diseases because of the lack of a suitable delivery method into the heart. Therefore, we compared the transfection efficiency of antisense oligodeoxynucleotides (ODN) using HVJ-liposome method and direct transfer in in vivo transfer into heart. To investigate the cellular fate and localization of ODN, transfer of "naked" FITC-labeled antisense ODN or ODN enwrapped in HVJ-liposome complex were examined. Following in vivo transfer using direct injection as well as in vitro transfer, fluorescence rapidly disappeared within 1 day, whereas transfer by HVJ-liposome method resulted in sustained fluorescence localized in the nucleus for at least 1 week. Measurement of fluorescence also demonstrated a significantly higher level in myocardium transfected by HVJ-liposome method than direct transfer. The present study demonstrated that HVJ-liposome method is more efficacious for ODN delivery by prolongation of half-life of ODN, suggesting its usefulness for gene therapy in cardiac diseases.