Researchers Develop Novel “Smart” Proteins Programmed To Turn Genes On And Off

Aiming to control the activity of genes and other molecules in living cells in predetermined ways, the researchers have created artificial proteins.

The advance can be used to program the behaviour of more complex chemical and biological systems.

In the study, published in the journal Science, the scientists showed that the designer proteins can regulate the activity of genes inside the human immune system’s T-cells, adding that the development may improve the safety and durability of future cell-based therapies.

The researchers, including those from the University of Washington in the US, explained that the proteins, like their electronic counterparts, logic gates, implement a Boolean function, which is a logical operation performed on one or more binary inputs that produces a single binary output.

They explained that these logic gates sense and respond to signals in predetermined ways.

Citing an example, the scientists said, the ‘AND’ gate produces output only when one input AND another are present.

When typing on a keyboard, pressing the Shift key AND the A key produces an uppercase letter A, they explained.

The novel protein logic gates, made from biological parts, aim to bring this level of control into bioengineered systems, the researchers added.

“Bioengineers have made logic gates out of DNA, RNA and modified natural proteins before, but these are far from ideal. Our logic gates built from de novo designed proteins are more modular and versatile, and can be used in a wide range of biomedical applications” said study senior author David Baker from the University of Washington.

Using proteins like the one currently developed, the scientists said, inputs such as the presence of two different molecules in a living cell can cause it to produce a specific output, such as activating or suppressing a gene.

“The whole Apollo 11 Guidance Computer was built from electronic NOR gates,” said lead author Zibo Chen, a recent UW graduate student.

“We succeeded in making protein-based NOR gates. They are not as complicated as NASA’s guidance computers, but nevertheless are a key step toward programming complex biological circuits from scratch,” Chen added.

While recruiting a patient’s own immune cells in the fight against cancer has worked for certain forms of the disease, targeting solid tumours with genetically engineered T-cells has proven challenging.

Based on earlier studies, the researchers believe this could in-part be due to T cell exhaustion.

Genetically altered T cells can fight for only so long before they stop working, they explained.

But with protein logic gates that respond to exhaustion signals, the scientists hope to prolong the activity of genetically modified T cells.

“Longer-lived T cells that are better programmed for each patient would mean more effective personalized medicine,” Chen said

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