Topical treatment wipes out herpes with RNAi

January 21, 2009

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."

These findings will be published in the January 22 issue of Cell Host and Microbe.

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.

By introducing tiny RNA molecules into cells, researchers can target a gene of interest and, in effect, throw a wrench into that gene's ability to build protein molecules. For all intents and purposes, that gene is now disabled.

While RNAi has profoundly accelerated the ability of scientists to probe and interrogate cells in the Petri dish, therapeutic breakthroughs have proved far more problematic. Researchers have had a difficult time delivering these tiny RNA molecules and ensuring that they actually penetrate the desired cells and tissues in a living organism.

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.

One RNA molecule in the topical solution targeted a herpes gene called UL29, which the virus needs to replicate. Knocking out UL29 inactivates the virus.

Another RNA molecule targeted Nectin-1, a surface protein found on cells in the vaginal tissue. Nectin-1 acts as a kind of host gatekeeper to which the virus binds to pass into the cell. Without Nectin-1, the virus simply can't infect cells.

Either RNA molecule delivered by itself would be sufficient to block the virus, but together in this RNAi cocktail, the host tissue becomes like a fortress that pulls up the drawbridge to block the enemy's entrance, and also has a full-fledged battle plan to slaughter the enemy if they make it through.

"As far as we could tell, the treatment caused no adverse effects, such as inflammation or any kind of autoimmune response," says Lieberman. "And while knocking out a host gene can certainly be risky, we didn't see any indication that temporarily disabling Nectin-1 interfered with normal cellular function."

Paper: Cell Host & Microbe, January 22, 2009, Vol 5 No. 1 "Durable Protection from Herpes Simplex Virus-2 Transmission Following Intravaginal Application of siRNAs Targeting Both a Viral and Host Gene"

Source: Harvard Medical School

Explore further: Targeting HIV's sugar coating: New microbicide may block AIDS virus from infecting cells

Related Stories

Targeting HIV's sugar coating: New microbicide may block AIDS virus from infecting cells

September 23, 2011
University of Utah researchers have discovered a new class of compounds that stick to the sugary coating of the AIDS virus and inhibit it from infecting cells – an early step toward a new treatment to prevent sexual ...

Ozone nano-bubble water is a potential treatment for severe gum infections

September 12, 2014
A powerful new antiseptic agent, called ozone nano-bubble water, holds promise for the treatment of periodontitis, or severe gum infections, according to research published in the journal Science and Technology of Advanced ...

Novel phage therapy saves patient with multidrug-resistant bacterial infection

April 25, 2017
Scientists and physicians at University of California San Diego School of Medicine, working with colleagues at the U.S. Navy Medical Research Center - Biological Defense Research Directorate (NMRC-BDRD), Texas A&M University, ...

New research explains why HIV is not cleared by the immune system

April 13, 2016
Scientists at the University of North Carolina (UNC) School of Medicine and Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a human (host) protein that weakens the immune response to HIV and other ...

Scientists explore alternative to antibiotics

July 15, 2011
A pioneering method for fighting burn infections in children using viruses which destroy disease-causing bacteria has been awarded new funding.

CRISPR genome editing and immunotherapy – the early adopter

April 24, 2017
It's been a couple of years since the genome editing tool CRISPR first hit the headlines. And talk of its potential to cure all manner of diseases, create superhumans and bring dinosaurs back from the dead has followed.

Recommended for you

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.