Genetically-engineered microorganisms could be useful for many things, if they can be controlled easily. Researchers have now developed a genetic kill switch that can be inserted into genetically-engineered microbes so they will self-destruct under a specific set of parameters. The work has been reported in Nature Communications.
Genetic circuits can be designed to sense environmental conditions and respond to them. Microbes might able to detect a molecule and move toward it, or identify an invader and destroy it. In the lab of Tae Seok Moon, an associate professor of energy, environmental and chemical engineering at Washington University in St. Louis, scientists have been designing microbes that will destroy themselves if the temperature around them gets to a certain point.
Genetically-engineered microbes that can be ordered to eliminate themselves might be more palatable for use because the risk they pose is lower.
Researchers in Moon's lab have been engineering microbes that will self-destruct when they sense a certain temperature, but there have been challenges. "But the previous work had either a base-level activation that was either too high or too low," Moon said. Once that problem was solved, "the bacteria would mutate." So, although the bacteria were supposed to die off when the temperature reached a set point, there would be many left alive. In some cases, the kill switch would also take too long to turn on, which gives the bacteria extra time to mutate.
While Moon wants to engineer microbes that can be used to break down plastic to help the environment, we would have to know how long the microbes will remain stable so they can finish the job. "It might be a few days, or a few weeks because we have so much waste," noted Moon.
By inserting several kill switches, the researchers were able to overcome these problems. With as many as four kill switches, tests using as many as a billion microbes indicated that none, or only a single cell, would survive. Daily tests of microbes that carried kill switches in their DNA revealed that the kill switches would function for as many as 28 days.
"This is the best kill switch ever developed," Moon said.
In this study, the researchers tested the engineered microbes in a mouse model, but in the future, Moon is interested in developing kill switches for microorganisms that can be applied to soil. Microbes like that might be created to destroy pathogens that harm crops, or one, day, for the microbiome in the human gut.
Ultimately, engineered microbes should be made to do what we want them to do, and then go away, said Moon. Microbes might be useful for solving various issues, he added. "They can be very smart as long as we teach them well."
Sources: Washington University in St. Louis, Nature Communications