Topical Treatment Wipes Out Herpes

Whether condoms or abstinence, most efforts to prevent sexually transmitted diseases have a common logic: keep the pathogen out of your body altogether. While this approach is certainly reasonable enough, it doesn't help the countless people worldwide who, for a number of reasons, are not in a position to control their sexual circumstances.

Now, Harvard Medical School professor of pediatrics Judy Lieberman, who is also a senior investigator at the Immune Disease Institute, has overseen the development of a topical treatment that, in mice, disables key genes necessary for herpesvirus transmission. Using a laboratory method called RNA interference, or RNAi, the treatment cripples the virus in a molecular two-punch knockout, simultaneously disabling its ability to replicate, as well as the host cell's ability to take up the virus.

What's more, the treatment is just as effective when applied anywhere from one week prior to a few hours after exposure to the virus. In that sense, the basic biology of this prophylactic enables a real-world utility.

"People have been trying to make a topical agent that can prevent transmission, a microbicide, for many years," says Lieberman. "But one of the main obstacles for this is compliance. 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. 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."

The World Health Organization estimates that approximately 536 million people worldwide are infected with herpes simplex virus type 2 (HSV-2), the most common strain of this sexually transmitted disease. Women are disproportionately affected. This is especially serious, since the virus can easily be passed from mother to child during birth, and untreated infants face risks of brain damage and death. While HSV-2 alone isn't life-threatening in adults, infection does increase a person's vulnerability to other viruses such as HIV.

In order for the herpesvirus to infect the host, two conditions must be met. First, the virus must be able to enter and take over host cells. Second, the virus must then reproduce itself.

Lieberman's topical treatment uses RNAi to foil both these events.

RNAi, a biological process that was identified barely a decade ago, has transformed the field of biological research. A breakthrough that earned the Nobel Prize in 2006, RNAi is a natural cellular process that occurs in all cells of all multicellular organisms to regulate the translation of genetic information into proteins. This natural process can be manipulated by researchers to switch off specific genes, and there is much research and development work to
harness RNAi for therapeutics.

Many in the field think RNAi-based drugs may be the next important new class of drugs.

In addition, Lieberman is investigating how this same approach might be used to treat HIV in a multi-institutional program funded by the National Institutes of Health that includes researchers at the Tulane National Primate Research Center, St. George's Hospital in London, and Alnylam Pharmaceuticals in Cambridge.