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Kamikaze Vaccine

26 January 1998 7:00 pm
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Scientists have turned a deadly bacterium into a suicide bomber of sorts that can drop a load of therapeutic genes into human cells, then harmlessly self-destruct. This method, described in next month's issue of Nature Biotechnology, could lay the groundwork for a versatile vaccine or novel gene therapy approaches.

For years, vaccine developers have tried to insert genes into immune cells called macrophages, which can carry out directed attacks on specific proteins. Werner Goebel and his colleagues at the University of Würzburg in Germany took a novel tack: They engineered the Listeria bacteria--a notorious contaminant of meat and dairy products--to turn one of its weapons on itself. When engulfed by macrophages, normal Listeria strains unleash an enzyme called listeriolysin that eats away at the holding cell inside a macrophage. By moving the gene encoding listeriolysin to a different part of the genome, the researchers forced Listeria to destroy its own cell membrane and spill its contents into the macrophage's cytoplasm.

After inserting a fluorescence gene into the disabled Listeria strain, Goebel's group showed that the bacteria could infect cultured human macrophage cells and destroy itself, leaving behind the fluorescence gene, which was taken into the macrophage nucleus in 0.2% of the cells. While a low percentage, that's enough for a successful vaccine, the researchers say.

The findings catapult Listeria into the ranks of other infectious organisms being tested as possible vaccines, including salmonella. "It's too early to rank one over the other," says Daniel Portnoy, a cell biologist at the University of California, Berkeley. He adds that Listeria is also promising as a potential delivery vehicle for gene therapy: "As we understand more about the molecules that Listeria uses to invade, we may be able to target it to different tissues."

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