Vaginal Treatment May Prevent Herpes
Topical Use of siRNAs Keeps Mice Herpes-Free; Approach Has Anti-HIV Potential
Jan. 21, 2009 -- Small anti-herpes RNA molecules applied to the vagina protect mice against new herpes simplex virus type 2 (HSV-2) infections for one week.
The preventive treatment uses small interfering RNA (siRNA) molecules. These tiny bits of genetic material are designed to switch off specific genes.
The herpes treatment uses two siRNAs. One keeps vaginal cells from producing a molecule that the herpes virus uses to infect cells. The other siRNA targets a viral gene required for herpes reproduction.
"One of the attractive features of the compound we developed is that it creates in the tissue a state that's resistant to infection, even if applied up to a week before sexual exposure," Harvard researcher Judy Lieberman, PhD, says in a news release. "This aspect has a real practicality to it. If we can reproduce these results in people, this could have a powerful impact on preventing transmission."
HSV-2 is the main cause of genital herpes. It's considered a sexually transmitted infection, although mother-to-infant transmission occurs during the birth process.
Researchers have long believed that herpes and HIV could be prevented by vaginal application of antiviral agents. But such "vaginal microbicides," even if effective, must be safe, non-messy, and long-lasting to be of real use to women.
Lieberman's team came up with an earlier version of their topical siRNA but found that the formulation they used actually encouraged herpes infection. Their current, two-pronged siRNA treatment avoids this problem -- at least in mice.
However, the same target they used in mouse vaginal cells -- a molecule called nectin-1 -- is also found on human vaginal cells. Blocking nectin-1 doesn't seem to harm mice. It may not harm humans, either, as the molecule seems to be needed during development but not during adult life.
That suggests the drug might not be safe during pregnancy. But if it works in sexually active adults, it would still be an enormous benefit to human health. An estimated 536 million people worldwide are infected with HSV-2. And HSV-2 infection makes it easier for a person to get infected with HIV.
Lieberman and colleagues suggest their siRNA approach might also work against HIV.
Their study appears in the Jan. 22 issue of Cell Host & Microbe.