Leor Weinberger calls it hijacking the hijacker.
In his lab at the Gladstone Institutes, he's developed a technique for harnessing stray bits of HIV - a virus that infects and ultimately kills immune cells - and using them to attack the virus itself.
His work, still preliminary and untested in animals or humans, is part of what some scientists are calling a "renaissance" in viral therapy. Giant advances in our understanding of how viruses work and how they can be manipulated have led to a growing field of research in using them to fight some of the world's deadliest diseases.
"We're building a therapy for HIV, because that's what we are experts in, but we believe this is not just HIV-specific," said Weinberger, an associate investigator at Gladstone.
Viruses now are being considered to fight bacterial infections and cancer, in addition to other viruses.
Using viruses to the advantage of humankind has been around for centuries, actually, starting with the advent of vaccines, which use weakened or dead viruses to trigger an immune response to an infectious disease.
Half a century ago, scientists recognized that some viruses seemed to naturally be attracted to and kill cancer cells, and doctors tried to harness those viruses and use them therapeutically. But the viral treatments couldn't be well controlled - patients sometimes became sick from the viruses, or if the treatment worked at first, the cancer almost always came back.
So for several decades, research into viral therapies all but disappeared, other than some vaccine studies. It was in the 1980s and '90s, during an explosion of scientific discovery into the basic mechanisms of viruses, that researchers began reconsidering the potential benefits.
Viruses are microscopic particles that rely on living organisms to replicate, and replication is one thing they excel at. Viruses infect cells and take over the cells' mechanisms, turning the hosts into factories to produce more of the virus, before eventually killing the cell.
Different viruses infect different types of cells. HIV, for example, infects immune cells, while cold and flu viruses infect cells in the respiratory tract. But one thing viruses have in common is their ability to insert their own genetic material into the DNA of the host cell, altering its function.
That trait alone has potential therapeutic uses. Imagine viruses as a Trojan horse of sorts - able to gain entrance into a human cell and deposit its genetic stash, good or bad.
"The strategy that viruses use is that they target a particular cell and they deliver this package of genetic information. If you can waylay that process, you can deliver in a precise way whatever package of genetic information you want," said Dr. Robert Siegel, a microbiologist and immunologist at Stanford. "That's what makes them appealing."
A role in gene therapy
Since 1990, scientists have been using viruses for gene therapy - altering a person's DNA to treat a disease - often to replace genetic mutations that are doing harm. Gene therapy hasn't yet become a standard of treatment, although there have been successful cases involving several different diseases in the past five years.
Even if gene therapy hasn't proved widely successful yet, scientists say our understanding of how viruses replicate and pass on genetic material has opened new avenues of research into how they can be harnessed in other ways.
Scientists now believe that they may be able to engineer viruses that target certain diseases, or that boost our own immune system when it's under attack from cancer. In fact, every virus that is studied for therapeutic benefits has been genetically modified in a lab. Some have been changed to be more focused in the types of cells they target, or to attack a disease on multiple fronts.
"Some of these viruses, they're like an iPhone - you can put in all these different apps," said Dr. David Kirn, chief medical director of San Francisco-based Jennerex, where he's studying the vaccinia virus to fight liver cancer.
"What if you had one product that could attack the cancer by multiple distinct mechanisms? Viruses can do it," Kirn said. "You can engineer in therapeutic payloads that attack by multiple mechanisms."
Kirn has engineered the vaccinia virus - which happens to be the same virus used in the smallpox vaccine - so that it has an affinity for cancerous cells, and once it attacks those cells it triggers the body's immune system to join the fight.
Virus vs. cancer
Like Kirn, many scientists believe that the most promising research in viral therapy is in cancer treatments. There's a natural connection between cancer cells and viruses - both are defined by their ability to rapidly replicate, for starters. That may be one reason some viruses are naturally drawn to tumors.
There have been some successes with cancer-fighting viruses, and Kirn said early clinical studies have shown liver cancer patients who are treated with his virus live a little longer than those who don't.
But viral therapies have yet to produce any sort of cure, and scientists aren't sure when or if they'll get there. Part of the problem with viruses is that they're living organisms themselves, and therefore somewhat beyond the control of doctors. Injecting a single-molecule drug into a patient can produce pretty standardized results, but a virus is more complex, and therefore difficult to apply expectations to.
Lately, scientists have been relying on mathematical models to predict how viruses will react in a human body, and those predictions have helped them determine when a virus is worth further study. But they hardly guarantee a positive outcome.
"When the first (cancer-fighting viruses) were developed, it felt like, this is the key to the Holy Grail right here," said Dr. Michael Korn, a UCSF oncologist.
He came to the United States from Germany as a visiting scientist 15 years ago, and worked with scientists who were studying viral therapies for cancer. That work was so thrilling that it persuaded him to stay in the U.S. - but his excitement has been tempered since then.
"The initial idea of using viruses is very simple and beautiful," Korn said. "Unfortunately, the reality is that it's much, much more complicated."
Still, scientists - including Korn - say the potential beneficial uses of viruses far outweigh the difficulties in studying them.
At Gladstone, Weinberger believes that his technique for hijacking HIV and using it against itself could help solve the global problem of treating the millions of people infected. Doctors have discovered several drugs that are very effective at treating HIV - patients who get the therapy and stick with it can expect to live almost a normal life span.
But the drugs are expensive, and not always easy to deliver to parts of Africa or other regions where HIV is widespread. Weinberger's therapy would address that problem, he says.
His technique focuses on stray bits of genetic material - called interfering particles - that are left behind when viruses replicate. The particles are like parasites and only able to replicate on the backs of HIV.
But Weinberger has engineered the particles to deposit a tiny bit of genetic material in cells infected by HIV. When those particles are injected into a host cell, that genetic material essentially replaces the material left by HIV, which means the HIV is no longer able to replicate.
His treatment, if it proves successful someday in humans, won't be a cure for HIV. But he believes a one-time dose of interfering particles may be enough to keep the virus from doing harm. And perhaps most important, the treatment itself would be infectious - the interfering particles, just like HIV, would be passed from person to person.
"The (interfering particles) will piggyback on the HIV and constantly evolve with it. You don't even have to give it to everybody," Weinberger said.
Weinberger admitted that he's not sure what kind of reception his plans will get from his scientific peers. He's only recently started publishing his research.
"It's a radical idea," he said. "The (HIV) hijacks a cell and turns it into a factory to produce more viruses. We're building parasites that can hijack that factory."
Erin Allday is a San Francisco Chronicle staff writer. E-mail: firstname.lastname@example.org