Unexpected payoffs from a bacterial immune system
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The tale of how a bacterial defense system against viruses became one of the most promising new platforms for genetic engineering and biotechnology also highlights the importance of basic research.
In 1987, researchers studying an enzyme that keeps intestinal bacteria like Salmonella out of the bloodstream discovered a curious set of segments of DNA containing short repetitions of base sequences, which they called CRISPR. Each repetition was followed by a “spacer DNA” segment from previous exposures to a bacterial virus or plasmid, which gave the bacteria “immunity” to that virus by allowing it to recognize and target this foreign intruder. Researchers began to investigate how to harness CRISPR’s power to “edit” DNA in animals, plants, and even human cells. Emory microbiologist David Weiss has taken that a step further—to affecting RNA.
Of the numerous types of CRISPR, Type II is the one that especially interests researchers such as Weiss. It requires only the action of RNA segments and one CRISPR associated protein, Cas9, making it significantly easier to use than the other types, which require multiple proteins. “We found Cas9 in our screen way before we understood what it did,” says Weiss, associate professor of infectious disease and a researcher at Yerkes National Primate Research Center. “When we pursued it, we found it knocks down the expression of specific RNA.”
Like the search function in a word processing program, Cas9 can be guided to specific locations within a complex genome by a short RNA search string.
“We can envision using Cas9-based technology to prevent viral infections in transgenic animals and plants,” Weiss says. “We could also re-engineer Cas9 to target RNA in human or other mammalian cells.”
