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Researchers turn Salmonella into anti-viral gene therapy agent

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New experiments at the University of California, Berkeley, may one day lead to anti-viral treatments that involve swallowing Salmonella bacteria, effectively using one bug to stop another.

Researchers at UC Berkeley’s School of Public Health have reprogrammed Salmonella, the same foodborne pathogen that can cause diarrhea, fever and abdominal cramps, into a safe transport vehicle for virus-stopping enzymes. Not only did this technique effectively treat mice infected with cytomegalovirus, it worked as an oral solution that was swallowed instead of injected.

Virologist Fenyong Liu teamed up with bacteriologist Sangwei Lu to develop the innovative technique, which is described in a study to be published online the week of Feb. 7 in the journal Proceedings of the National Academy of Sciences.

“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 Liu, a UC Berkeley professor at the Division of Infectious Diseases & Vaccinology.

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.

“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,” said Lu, a UC Berkeley associate adjunct professor at the Division of Infectious Diseases & Vaccinology. “Moreover, there is already an attenuated strain of Salmonella with a decent track record for safety in humans since it is now used in the vaccine for typhoid (a disease caused by Salmonella Typhi).”

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. CMV infections are generally mild among healthy individuals, but they can become deadly for people whose immune systems are compromised and are a leading viral cause of mental retardation in newborns.
 
 

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