A Breakthrough in Gene Editing Offers Hope for a Cure for Cold Sores

This piece is part of “The Cure for Everything:” A series of stories that looks at the breakthroughs, setbacks, and overall status of vaccines and cures for hard-to-treat diseases and viruses, from HIV and herpes to the flu and hangovers.

COLD SORES HAVE a way of appearing at the worst possible moments, like right before a big work presentation or a family photoshoot. That watery, tingly blister on your lip is a cruel reminder that you have, at some point, been infected with herpes simplex 1 or 2, viruses that usually lies dormant within your body.

You can use antiviral medication to put the brakes on an outbreak, but this virus, which infects about two-thirds of adults under 50 worldwide, has no cure. Herpes just keeps coming back, just like George Carlin said. Here’s why herpes has stumped guys from Ancient Greece to today—and the latest science on prevention and minimizing symptoms.

How the Stealth Virus Infects

The virus behind most oral herpes infections, herpes simplex 1, is highly contagious. It spreads through saliva, often through kissing, especially when an infected person has active sores (although it can be passed on even when they don’t). Herpes simplex 2, the virus usually responsible for genital herpes, can cause oral herpes infections, too—you might imagine how.

Once infected with oral herpes, most people show no symptoms. Others have their first outbreak within days. Unfortunately, many people (even doctors) don’t recognize the first sores as herpes. They forget about them in a week or so when their skin looks fine again. The problem is your body will not forget.

“That first infection seeds a ganglion along your spine, which is along the nerves on your back along the backbone,” says Robert T. Brodell, M.D., Professor and Chair, Department of Pathology at University of Mississippi Medical Center. Herpes simplex 1 has a favorite spot: the trigeminal ganglion, a cluster of nerve fibers that sits right behind your face.

As it nestles in, herpes goes into stealth mode, known as latency or dormancy. “The virus is able to hide for our lifetime inside the cells of our nervous system, and it hides in those cells actually as its DNA,” says David A. Leib, Ph.D., Chair and Professor of Microbiology and Immunology at Dartmouth Geisel School of Medicine. While the virus’s DNA is tangled up with yours, the virus doesn’t replicate. “During this latent period, the virus remains pretty inaccessible to immune attack, or to any kind of therapeutic attack, any kind of antiviral drug,” he says.

Herpes then stays quiet until something, usually stress, reactivates it. (That’s why Liz Lemon got cold sores when she was overwhelmed on 30 Rock.) One theory is that when the virus’s genome activates, cells containing DNA that isn’t as tightly entangled as others go into overdrive. Then, the virus rapidly releases proteins that confuse your cells’ immune responses. The virus starts replicating quickly and following the nerve’s pathway, bringing a new sore to the surface. Usually, the road leads from the trigeminal ganglion to the edge of your lip, although sores can crop up elsewhere, like the roof of your mouth or even in your eyes.

“This is sort of the ultimate relationship of a lifetime,” says Leib. “The virus just will hole up in the nervous system, and then periodically will come out sort of sneak attacks, if you will, in a so-called reactivation event, and this is what causes so much misery.”

Outbreaks usually strike the same spot one to five times per year and can be caused by stress, sun exposure, an injury and other causes. Prescription antiviral medications slow down viral replication so sores heal faster, but no drug can eliminate the virus entirely. “We simply cannot figure out how to get rid of that latent herpes DNA that sits in our nervous systems,” says Leib.

Or, as Dr. Brodell puts it, “these darn viruses are smart, and they’re sneaky.”

The Quest for the Next Breakthrough

Cold sores were first described by the Greek philosopher Herodotus in the fifth century BC, and the first modern pharmaceuticals for herpes came two and a half centuries later. The biggest development came in 1974 with the discovery of acyclovir—the first medication in a class called synthetic nucleoside analogs. This family of drugs, which now includes valacyclovir and famciclovir, are still the mainstay of herpes treatment today.

Scientists, healthcare providers, and infected people around the world, however, are hoping for a break in that 50-year slump in innovation. Herpes infections are annoying, sometimes embarrassing, and often stigmatized. What’s more, recent studies suggest oral herpes might be even more insidious, increasing long-term risk of health problems like head and neck cancers and Alzheimer’s disease. Researchers do not know exactly why, but it likely due to increased inflammation and stressing the body’s immune response. The possibility that herpes infections increase the risk of other diseases makes the search for a cure even more urgent, says Leib.

For now, researchers at universities and companies are working on vaccines and other approaches to prevent infection and help people who are already infected manage outbreaks. Even the government is picking up the pace. The U.S. Department of Health and Human Services initially left herpes out of its first Sexually Transmitted Infections National Strategic Plan for 2024, but after a push from patient advocates, they issued an addendum outlining strategies to prevent new infections, help people manage infections, accelerate innovation, reduce disparities and health inequalities related to herpes infections, and better coordinate efforts to understand the prevalence of infections.

Unfortunately, vaccine development efforts to date have largely flopped. “There is a veritable graveyard of herpes vaccines that have been tried and failed in clinical trials, and these have mostly failed because they have been unable to prevent transmission of the virus from one person to another,” says Leib. One factor could be the virus’s persistence. “It hangs out in the host forever and has many, many opportunities over the lifetime of a human to reactivate and be shipped to the community,” says Leib.

Today, pharmaceutical companies BioNTech, Moderna, and GlaxoSmithKline are conducting early-stage clinical trials for vaccines against herpes simplex 2, the variety more commonly associated with genital infections.

Some researchers are also looking at repurposing existing vaccines. In a study published in eClinicalMedicine, researchers revealed that men with frequent, recurrent cold sores who received the bacille Calmette-Guérin (BCG) vaccine, a shot usually used to prevent tuberculosis, had fewer cold sores than those in the control group. The cold sores they got didn’t last as long and were less severe, too.

Many of the most innovative treatments for oral herpes, however, are still in the early stages and being tested on animals. One novel approach, says Leib, is gene therapy to essentially edit out herpes simplex DNA. Researchers at Fred Hutchinson Cancer Center recently showed that by injecting herpes-infected mice with gene editing molecules delivered via harmless adenoviruses, they damaged the herpes virus DNA and eliminated 90 percent of oral herpes within a month. Clinical trials in humans will come in the next few years.

How to Handle Cold Sores Today

If you think you’re in the clear.

Avoided oral herpes to this point? Consider yourself lucky. You risk it anytime you hook up with someone new. You’re highly unlikely to contract herpes in more casual situations, although the virus can live on a toothbrush for two hours, in food for about an hour, and on some surfaces for 24 hours or more. Consider this another reminder to practice commonsense hygiene like washing your hands and using your own toothbrush.

If you think (or know) you have oral herpes.

If you haven’t already, ask your healthcare provider to swab your sores and order a polymerase chain reaction (PCR) test that detects the virus’s DNA. If you’re asymptomatic, you can get a PCR blood test instead, but the false positive rate is high, so some docs don’t recommend it.

If the results are positive, your doctor will prescribe antivirals you can take anytime symptoms start. If you know you always get outbreaks in certain situations, you can even take the medication ahead of time—Dr. Brodell calls this intermittent therapy. “If you’re the person where every time you go to the beach, you get sunburned, the herpes comes out, and it ruins your vacation, well, they start taking their pill, like a suppressive dose, one pill a day, the day before they get on the plane to go to the Bahamas. Take it through the time they’re at the Bahamas, and stop it when they’re done,” he says.

The antiviral acyclovir (sold as Sitavig, Zovirax) is also available as an ointment applied six times a day. “The problem with that is it doesn’t work as well as the oral treatments and the oral treatments are very safe and very convenient, and less messy,” says Dr. Brodell. But the cream is a good option for anyone who can’t take the oral medicine, like people with certain kidney problems.

For some, a pill and cream combo might be the best bet. A recent study review in the Journal of Evidence-Based Dentistry suggests that the combination of oral valacyclovir and topical clobetasol, a corticosteroid commonly used to treat skin conditions like eczema and psoriasis, heals cold sores faster than other treatments.

And if you can get a prescription quickly during your first outbreak? It’s not proven, but theoretically possible, that by treating your first outbreak with an antiviral within 48 hours of first developing blisters, you might be able to prevent the virus from making it to a ganglion and causing future recurrences, says Dr. Brodell. Plus, “it will heal faster, so there’s a reason to treat properly anyway,” he says.

You might also see the dietary supplement lysine touted as a remedy to help cold sores heal. Some scientific research suggests it could have antiviral effects, but in practice, the prescription stuff works better. “I’ve had hundreds of patients that never took lysine again, once they saw how well these treatments work,” says Dr. Brodell.

And PSA: Don’t kiss newborn babies faces. Their immune systems can’t contain the infection as well as ours can, so they can get extremely sick.

Read more stories in this special package that looks at the latest breakthroughs for common health issues.