title: Limited use of cationic liposomes as tools to enhance the antiherpetic activities of oligonucleotides in vero cells infected with herpes simplex virus type 1.
abstract: We used commercially available cationic liposomes, lipofectin, DOTAP, and transfectam, to enhance the antiherpetic activities of phosphodiester oligonucleotides (D-oligos) or phosphorothioate oligonucleotides (S-oligos) targeted against immediate-early pre-mRNA4/5 of herpes simplex virus type 1 (HSV-1). With a 5-fold excess of S-oligos/D-oligos, formation of complexes with some of the S-oligos/D-oligos and the cationic liposomes could be visualized on agarose gel. A >5-fold excess of cationic liposomes enhanced the antiherpetic activities of Doligos, whereas there was not enhancement of the antiherpetic activities of S-oligos. As nuclear localization of D-oligos in the presence of cationic liposomes was not clear, we could not clarify the relation between antiherpetic activities of D-oligos and nuclear distribution of oligos. Subcellular distribution of S-oligos in the presence of lipofectin or DOTAP showed nuclear localization by confocal laser scanning microscopy. Transfectam had no effect on the nuclear distribution of S-oligos. These data showed that cationic liposomes would not be appropriate carriers to enhance the antiherpetic activities of S-oligos. Also, distribution of S-oligos into the nucleus does not necessarily enhance their biologic activity. Questions remain about the effectiveness of cationic liposomes in the enhancement of the antivirus activity of S-oligos.
authors.affiliation: Institute of Medical Science, and Department of Microbiology, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shoji
authors.forename: M
authors.initials: M
authors.lastname: Norimatsu
authors.forename: J
authors.initials: J
authors.lastname: Shimada
authors.forename: Y
authors.initials: Y
authors.lastname: Mizushima
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001483:Base Sequence; D002412:Cations; D002522:Chlorocebus aethiops; D004337:Drug Carriers; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D008081:Liposomes; D009841:Oligonucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000378:metabolism; D013873:Thionucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D009841:Oligonucleotides; D013873:Thionucleotides