Batteries Prove to be the Missing Link Between Analogue and Digital Gene Expression

Monday - August 14 2023, 23:51 UTC - 1 year ago

A Swiss research team has developed an interface that uses household batteries to control gene expression in cells. The interface, which works with lab-made genes inserted into living cells, has already had an impact in a proof-of-concept test using mice with Type 1 diabetes. The interface's potential in wearables to directly guide therapeutics for metabolic and potentially other disorders is very promising, as three AA batteries could trigger a daily insulin shot for more than five years.

The components sound like the aftermath of a shopping and spa retreat: three AA batteries. Two electrical acupuncture needles. One plastic holder that’s usually attached to battery-powered fairy lights. But together they merge into a powerful stimulation device that uses household batteries to control gene expression in cells.The idea seems wild, but a new study in Nature Metabolism this week showed that it’s possible .

The team, led by Dr. Martin Fussenegger at ETH Zurich and the University of Basel in Switzerland, developed a system that uses direct-current electricity—in the form of batteries or portable battery banks—to turn on a gene in human cells in mice with a literal flip of a switch.To be clear, the battery pack can’t regulate in vivo human genes. For now, it only works for lab-made genes inserted into living cells .

Yet the interface has already had an impact. In a proof-of-concept test, the scientists implanted genetically engineered human cells into mice with Type 1 diabetes. These cells are normally silent, but can pump out insulin when activated with an electrical zap.The team used acupuncture needles to deliver the trigger for 10 seconds a day, and the blood sugar levels in the mice returned to normal within a month .

The rodents even regained the ability to manage blood sugar levels after a large meal without the need for external insulin, a normally difficult feat.Called "electrogenetics," these interfaces are still in their infancy. But the team is especially excited for their potential in wearables to directly guide therapeutics for metabolic and potentially other disorders. Because the setup requires very little power, three AA batteries could trigger a daily insulin shot for more than five years, they said .

The study is the latest to connect the body’s analogue controls—gene expression—with digital and programmable software such as smartphone apps. The system is "a leap forward, representing the missing link that will enable wearables to control genes in the not-so-distant future," said the team.The Trouble With Genetic ControlsGene expression operates in analogue. DNA has four genetic letters (A, T, C, and G), which are reminiscent of a computer’s 0s and 1s .

However, the genetic code can’t build and regulate life unless it’s translated into proteins. The process, called gene expression, recruits dozens of biomolecules, each of which is controlled by others. "Updates" to any genetic circuits are driven by evolution, which works on notoriously long time scales. While powerful, the biology playbook isn’t exactly efficient.Enter synthetic biology. The field assembles new genes and taps into cells to form or rewire complex circuits using the logic of machines .

Early experiments showed that synthetic circuits can control biological processes that normally result in cancer, infections, and pain. But activating them often requires molecules as the trigger—antibiotics, vitamins, food additives, or other molecules—keeping these systems in the realm of analogue biological computing.Neural interfaces have already bridged the divide between neural networks—an analogue computing system—and digital computing networks .

Programmable components, such as transistors, were the missing link. Batteries are now doing the same for gene circuits.