Development of targeted, reliable and long-lasting gene kill switches

Associate Professor Te Suk Moon is developing a bacterial kill switch to allow bacteria to work and then self-destruct. He finally plans to use such a switch with the bacteria used to detect and treat diseases of the human body.Credits: Washington University in St. Louis

Tesok Moon, an associate professor of energy, environment, and chemical engineering at McKelby’s Faculty of Engineering at the University of Washington in St. Louis, takes a major step in his quest to design a modular, genetically engineered kill switch that integrates into every gene. I did. Genetically engineered microorganisms self-destruct under certain defined conditions.

His study was published in the journal on February 3rd. Nature Communications..

Moon lab understands Microorganisms In a way that only engineers do, like a system consisting of sensors, circuits, and actuators. These are the components that allow microorganisms to sense the world around them, interpret it, and act on that interpretation.

In some cases, actuators may move informedly by moving towards a particular protein or attacking a foreign intruder. Moon is developing actuators that resist the millions of years of evolution that have acted in favor of self-preservation, instead instructing microorganisms to self-destruct.

The Emergency stop device Activators are an effort to alleviate concerns about the potential for genetically modified microorganisms to invade the environment. So far, he has done some development. For example, when the surrounding environment reaches a certain temperature, it self-destructs microorganisms.

“But the previous work had a base-level activation that was too high or too low,” Moon said. And every time he solves the problem, “the bacteria will mutate.” During the experiment, it meant that too many microbes survived after the kill switch was supposed to be on.

In addition, in some situations the kill switch may not be triggered for several days. This additional time represents an additional opportunity for the microorganism to mutate and can affect the ability of the switch to operate.

For example, Moon is interested in developing microorganisms that have been genetically engineered to eat plastic as a way to dispose of harmful waste. “But we don’t know how many days it will take to stabilize these microbes until the cleanup of the environment is complete. It may take days or weeks, because of the sheer amount of waste,” Moon said. He said.

To overcome these obstacles, Moon inserted multiple kill switches (up to four) into the DNA of the microorganism. Results: During the experiment, only one or none of the billion microbes may survive.

During the experiment, researchers tested the microbes daily. The switch continued to function for 28 days.

“This is the best killing switch It has been developed so far. “

These experiments were also performed on mice, but in the future, the Moon hopes to build a kill switch for microorganisms used in soil. It is probably used to kill pathogens that are deadly to crops, or even to cure the disease in the human intestine.

The final game is to let the microbes do what we want to do and then leave, Moon said. He believes that these microbes can be used to solve a host of global problems. “Bacteria may look silly, but as long as we teach them well, they can be very smart,” he said.

A new type of kill switch to prevent GM microorganisms from causing havoc

For more information:
Austin G. Rottinghaus et al, a genetically stable CRISPR-based kill switch for genetically engineered microorganisms, Nature Communications (2022). DOI: 10.1038 / s41467-022-28163-5

Quote: Https: // Developed on February 9, 2022 to develop a targeted, reliable and long-lasting gene kill switch. (February 9, 2022)

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Development of targeted, reliable and long-lasting gene kill switches

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