New tools for turning genes into drug factories

DNA
Specially designed gene promoters could be used to construct complex circuits that can produce drugs in the body on demand.

Synthetic biologists have long dreamed of designing genetic circuits in the body that can produce drugs in response to environmental cues. But it’s been a challenging task. Now scientists at Rice University say they’ve created a toolkit of gene “promoters” that can turn genes on and off at command.

They made the promoters using the bacteria E. coli, according to a press release from the university. Working with mathematicians from the University of Houston, the Rice team developed a library of promoters, each of which can react in specific ways to chemical inputs.

One gene can be programmed to produce a specific protein in the presence of a particular chemical, for example, which can then become the cue for another gene to turn on or off. They described their invention in the journal Nature Communications.

Naturally occurring gene promoters are often “leaky,” meaning that even when they turn a gene off, that gene continues to produce a protein. So the researchers set out to create promoters that would allow for the construction of complex but very precise gene circuits.

"Nature gives us only a few examples of promoters that use multiple inputs, so designing nonleaky, easy-to-use multi-input promoters was a high priority for us," said study co-author Matthew Bennett, associate professor of biosciences at Rice, in the statement.

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Scientists at the Massachusetts Institute of Technology are also designing technologies for gene circuits, but theirs are inspired by electronics. In October, an MIT team described promoters they developed that can be delivered to tumor cells, where they activate genes to produce immune-boosting proteins. They believe their concept could be applied not just to cancer, but also to autoimmune disorders like inflammatory bowel disease.

One area where the Rice scientists believe their promoters could prove useful is in the design of probiotics—beneficial gut bacteria that are being investigated for their potential to aid in the treatment of many diseases. Promoters that can turn genes on and off in a circuit could “act as sensors, allowing the probiotic to produce the drug when it is needed based on environmental cues," Bennet explained.

In their journal article, the researchers suggested that if their promoters were used in conjunction with technologies that control the rate of production of proteins, it could “provide exquisite control over the dynamic range of gene expression in synthetic gene circuits.”