Salmonella Engineered to Deliver Gene Therapy

Researchers at the University of California, Berkeley, transformed salmonella bacteria, best known for its ability to cause food poisoning, into a virus-fighting tool. Starting with a weakened form of the bacteria, the scientists engineered it to carry a virus fighting particle. Salmonella make particularly good carriers because they can be taken orally—the microbes evolved to survive in the harsh environment of the human digestive system—and they can effectively deliver the antiviral molecules into infected cells.

Mice infected with a type of the herpes virus called cytomegalovirus and treated with the engineered salmonella survived twice as long their untreated counterparts.

According to a press release from the university,

“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).”

FDA Sites Drug Makers that Fail to Finish Follow-up Studies

In order to speed access to potentially life-saving medicines, the U.S. Food and Drug Administration sometimes grants accelerated approval to experimental drugs before completion of large-scale clinical trials. Drugmakers then agree to continue research on the drug to confirm its benefits in patients. But that doesn’t always happen in a timely manner. At a public meeting earlier this week, the FDA questioned companies that make six cancer drugs, about their failure to finish follow-up studies. According to an article in the Wall Street Journal,

The FDA can fine companies millions of dollars or revoke approval if the evidence isn’t forthcoming. At Tuesday’s meeting, FDA officials stopped short of making those threats against the companies making the six drugs—which include Amgen Inc., GlaxoSmithKline PLC and Eli Lilly & Co.—but spoke generally about the value of timely confirmation.

“These confirmatory trials are as important—if not more important—than the initial trials leading to the accelerated approval,” said Richard Pazdur, the head of the FDA’s cancer division. He said some companies have taken more than six years to complete the trials.

…In five cases, studies failed to confirm benefit and drugs were withdrawn or faced new restrictions, according to the FDA. That happened in 2005 to AstraZeneca PLC’s lung-cancer drug Iressa, which failed to show survival benefit in a large trial and was pulled except for patients already on the drug.

RNA Interference Loses its Luster

An article in the New York Times argues that pharmaceutical companies are losing interest in RNA interference (RNAi), a Nobel prize winning technology to silence genes. Drug makers had hoped that RNAi would provide a way to target proteins not easily altered with small molecule drugs. According to the New York Times,

The biggest bombshell was dropped in November, when the Swiss pharmaceutical giant Roche said it would end its efforts to develop drugs using RNAi, after it had invested half a billion dollars in the field over four years. Just last week, as part of a broader research cutback, Pfizer decided to shut down its 100-person unit working on RNAi and related technologies. Abbott Laboratories has also quietly shelved its RNAi drug development work.The issue is that while drugs working through the RNAi mechanism can indeed shut off genes, it has been difficult to deliver such drugs to the cells where they are needed. At a time when hard-pressed pharmaceutical companies are already scaling back research expenditures, RNAi is losing out to alternatives that seem closer to producing marketable drugs.