Diarrhea-causing bacteria turned into antiviral gene therapy agent

WASHINGTON - New studies conducted by researchers at the University of California, Berkeley, could one day lead to anti-viral treatments that involve swallowing Salmonella bacteria, effectively using one bug to stop another.

The researchers have reprogrammed Salmonella, the same foodborne pathogen that can cause diarrhea, fever and abdominal cramps, to safely transport virus-stopping enzymes into cells without causing disease.

Not only did this technique effectively treat mice infected with cytomegalovirus, it worked as an oral solution that was swallowed instead of injected.

“A number of vaccines, including those for polio and smallpox, use live but weakened viruses to build up the immune system. But this is the first time anyone has successfully engineered bacteria for treatment of a viral infection,” said Fenyong Liu, of the UC Berkeley.

The researchers said Salmonella was particularly appealing because it has evolved to survive the human digestive system, allowing it to be swallowed instead of injected or inhaled.

Sangwei Lu of the UC Berkeley said, “This is the first gene therapy treatment for viral infection that can be taken by mouth, which is far more convenient to administer than an injection.”

Researchers know that ribozymes, enzymes that are able to target and cut specific RNA molecules, can be used to inactivate a pathogen’s genes. But to do their work, ribozymes need to first get into the cells, and for that they need help.

It so happens that Salmonella is very good at invading cells, so the researchers found a way to use the bacterium as a vector for the RNase P ribozyme that could stop the gene activity of cytomegalovirus, or CMV.

CMV is in the same family of herpes viruses that causes cold sores, mononucleosis and chickenpox.

Previous research by Liu and Lu showed that Salmonella could effectively sneak the anti-viral ribozymes into human cells infected with human cytomegalovirus and reduce the viral load of the cell cultures. This new study put the technique to the test in living mice.

Moreover, the researchers found that the viral load of mice treated with the ribozyme-carrying Salmonella was 400- to 600-times lower than the viral load for mice given the defective ribozymes and for mice that were untreated.

The researchers pointed out that using bacteria instead of viruses as gene-therapy vectors has a number of advantages.

The findings have been published in the journal Proceedings of the National Academy of Sciences. (ANI)