Topical treatment wipes out herpes with RNAi

Thursday, January 29th, 2009

A new topical treatment wipes out herpes with RNAi:

Harvard Medical School researchers have succeeded in developing a topical treatment that, in mice, wipes out herpes virus, one of the most intractable sexually transmitted human diseases.

Judy Lieberman, professor of pediatrics and a senior investigator at the Immune Disease Institute, has overseen the development of the treatment that uses RNA interference, or RNAi, to disable key genes necessary for herpes virus transmission. That 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.”

RNA interference is still a fairly new discovery, and drug delivery still poses a challenge:

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 current research and development work to harness RNAi for therapeutics.
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Modifying a delivery technique that Lieberman developed in 2005, she and postdoctoral fellow Yichao Wu and junior researcher Deborah Palliser (who now heads her own laboratory at Albert Einstein College of Medicine) treated mice with strands of RNA that were fused to cholesterol molecules, which made it possible for the molecules to pass through the cell membranes. When applied in the form of a topical solution, these RNA molecules could then be fully absorbed into the vaginal tissue, protecting the mice against a lethal dose of administered virus.

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