New Salmonella strain delivers gene-based therapy to fight virus in mice

Most people do their best to avoid contact with Salmonella. This bacteria genus, which often lives on poultry and can find its way intoother food products, causes hundreds of thousands of illnesses—and hundreds of deaths—in the U.S. each year. But new research demonstrates that this common food pathogen could be disarmed and reconfigured as a vehicle for gene-based antiviral treatments.

In the past two decades, scientists have developed gene-based therapies that rely on viruses to deliver key genetic material to the body's cells. But concerns have been raised about the safety of this technique—and its effectiveness in delivering the desired material to the proper cellular targets. Nevertheless, viruses are familiar biomedical tools, having been used in weakened or killed form in vaccines for decades.

Now, a team of scientists has studied whether bacteria, in particular Salmonella, might make better assistants in fighting disease at the genetic level.

Commonplace bacteria are logical candidates for this work, being well adapted to living in the human body, invading our cells and transferring genetic material to them. If a bacterium's illness-inducing qualities can be dialed back, it could be useful in carrying genes to fend off some viral infections.

"This is the first time anyone has successfully engineered bacteria for treatment of a viral infection," Fenyong Liu, a University of California, Berkeley virologist who worked on the new research, said in a prepared statement. The research team found that altered Salmonella were effective in preventing severe infection withcytomegalovirus (CMV)—a widespread virus that can cause severe complications for newborns and people with compromised immune systems. There is currently no approved vaccine for CMV.

The new method, demonstrated in mice, is described in a paper published online Monday in Proceedings of the National Academy of Sciences. Mice infected with a murine strain of CMV and given oral doses of the altered bacteria were found to live longer than infected counterparts that did not receive the therapy. Research has shown that small interfering RNAs and ribozymes can muck up viral proteins involved in replication in host cells. And the new study demonstrated that an RNA enzyme plugged into the new strain of Salmonella helped block CMV infection in key organs, such as the liver and spleen.

Weakened strains of Salmonella are already used to vaccinate against typhoid, which is caused by a form of Salmonella infection. And researchers had previously shown that these virus-busting ribozymes could be introduced into Salmonella, but the new study shows for the first time that the bacteria were effective in delivering the introduced RNA enzyme to targeted cells in live animals.

If the Salmonella strategy continues to prove successful in additional animal experiments, bacteria of other types could be assayed to replace viruses as vehicles for some genetic therapies. Viruses can be tricky to maintain in the lab and contamination has been a concern, but "to grow bacteria, you need only add some bacteria to a simple medium, and the next day you can have 100 billion bacteria ready to go. It's safer, easier and cheaper as a vector for gene therapy," Sangwei Lu, a bacteriologist at Berkeley and co-author of the new study, said in a prepared statement.

Bacteria can present their own problems in the lab, of course, and the research still has a long way to go before we will be intentionally swallowing doses of Salmonella. In the meantime, despite efforts to improve food safety, the bacteria remain armed and at large in the food supply.

Image of Salmonella courtesy of CDC/Bette Jensen