title: In vivo transfer efficiency of antisense oligonucleotides into the myocardium using HVJ-liposome method.
abstract: 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.
authors.affiliation: Department of Geriatric Medicine, Osaka University Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Aoki
authors.forename: R
authors.initials: R
authors.lastname: Morishita
authors.forename: J
authors.initials: J
authors.lastname: Higaki
authors.forename: A
authors.initials: A
authors.lastname: Moriguchi
authors.forename: I
authors.initials: I
authors.lastname: Kida
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Matsushita
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneda
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D008081:Liposomes; D009206:Myocardium / Q000201:enzymology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018108:Respirovirus
chemical_list: D008081:Liposomes; D016376:Oligonucleotides, Antisense; D007703:Peptidyl-Dipeptidase A