Limited use of cationic liposomes as tools to enhance the antiherpetic activities of oligonucleotides in vero cells infected with herpes simplex virus type 1.
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.
Shoji
Y
Y
Institute of Medical Science, and Department of Microbiology, St. Marianna University School of Medicine, Kawasaki, Japan.
Norimatsu
M
M
Shimada
J
J
Mizushima
Y
Y
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
D000998:Antiviral Agents; D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D009841:Oligonucleotides; D013873:Thionucleotides