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Small RNA Molecules Tackle Herpes

on 23 November 2005, 12:00 AM | | 0 Comments
Picture of herpes virus
Wily enemy.
Herpes simplex virus evades most attempts to kill it, but a new ointment helps infected mice.
Credit: Frederick A. Murphy at UC Davis

Efforts to stop the spread of sexually transmitted diseases (STDs) often fail because people don't take precautions in the heat of the moment. In an encouraging new development, researchers have designed and tested a topical therapy in mice that prevents infection by one of the most prevalent STDs, genital herpes virus, for days after it is applied.

Twenty percent of American adults are infected with herpes simplex virus type 2 (HSV-2), the virus that causes genital herpes. There are few effective treatments for the infection, which causes periodic outbreaks of painful genital sores, and no foolproof way to prevent transmission during sexual contact, although condoms can reduce the risk significantly. On its own, herpes is unpleasant but not life-threatening; however, people with herpes are especially vulnerable to HIV infection.

Judy Lieberman and her colleagues at Harvard Medical School drew on their experience using small RNA molecules, called small interfering RNAs (siRNAs), to blunt gene expression to create a novel antiviral that blocks HSV-2 infection in mice. As reported online today in Nature, they first designed several siRNAs based on sequences from the HSV-2 genome. The group then mixed the siRNAs with a type of fat molecule and applied it topically to the genitalia of 20 female mice, where the siRNAs readily entered cells of the vagina and cervix. When the treated mice were subsequently exposed to HSV-2, the siRNAs thwarted infection by binding to and destroying the RNA of the virus.

The treatment allowed 75% of mice to survive a level of HSV-2 exposure that is normally lethal. The animals' cells also retained the siRNAs for at least 9 days after application. In some experiments, the siRNA protected the mice even when applied several hours after HSV-2 exposure.

Biochemist and molecular biologist Sailen Barik of the University of South Alabama College of Medicine in Mobile views the work as evidence that siRNAs have the potential to combat herpes. But he cautioned that the treatment used represented very high dosages, and that researchers need to test its safety and efficacy at lower levels. Also, an effective and discreet therapy could be especially beneficial in societies where women have little control over their reproductive health, he added.

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