Enhancement of anti-herpetic activity of antisense phosphorothioate oligonucleotides 5' modified with geraniol.

Shoji Y, Ishige H, Tamura N, Iwatani W, Norimatsu M.

Institute of Medical Science, St. Marianna University, School of Medicine, Kawasaki, Japan.

We have previously shown that antisense phosphorothioate oligonucleotide (SON) targeted against immediate early (IE) pre-mRNA5 of the herpes simplex virus type I (HSV-I) possessed potent anti-herpetic activities in vitro system. However, anti-herpetic activities of SON were not still efficient enough. Lipophilic compounds have been often conjugated with antisense oligonucleotide to enhance the biological activity.

In this study, we selected geraniol as a lipophilic compound and newly synthesized SON bearing 5' terminal geraniol (geranyl-SON) toward IE pre-mRNA 5 of the HSV-1 to enhance the anti-herpetic activity.

Geraniol is a olefinic terpene alcohol which is found in many essential oils (some of which are found in H-Away). It possesses lipophilic characteristic. It is thought to be absorbed in tissue.

Geraniol enhanced the anti-herpetic activity of SON with less cytotoxicity in a sequence specific manner. Terminal modification with geraniol did not affect binding affinity with complimentary DNA. Cytoplasm distribution of geranyl-SON was confirmed by confocal microscope. While some of the geranyl-SON was seen in the nucleus, unmodified SON had a punctate distribution in the cytoplasm with little in the nucleus.

These results suggested that geranyl modification enhances anti-herpetic activity by changing the subcellular distribution of the oligonucleotides. Consequently geraniol-modifica-tion could provide new means for the efficient delivery of oligo-nucleotides.

PMID: 9713976 [PubMed - indexed for MEDLINE]

Our Conclusion: the anti-viral constituent geraniol in H-Away is able to penetrate into cell membranes to safely inactivate HSV1 (cold sores, fever blisters).