Artificial proteins that function as molecular logic gates

Turning cells into computers with protein logic gates.

Scientists at the University of Washington School of Medicine have devised artificial proteins that can regulate gene expression inside human T-cells. What’s interesting, these proteins can function as molecular logic gates, tools are used to program the behavior of more complex systems.

Senior author David Baker, professor of biochemistry at the UW School of Medicine and director of the Institute for Protein Design, said, “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.”

“Whether electronic or biological, logic gates sense and respond to signals in predetermined ways. One of the simplest is the AND gate; it produces output only when one input AND another are present.”

“For example, when typing on a keyboard, pressing the Shift key AND the A key produces an uppercase letter A. Logic gates made from biological parts aim to bring this level of control into bioengineered systems.”

“With the right gates operating inside living cells, inputs such as the presence of two different molecules—or one and not the other—can cause a cell to produce a specific output, such as activating or suppressing a gene.”

Lead author Zibo Chen, a recent UW graduate student, said, “The whole Apollo 11 Guidance Computer was built from electronic NOR gates. We succeeded in making protein-based NOR gates. They are not as complicated as NASA’s guidance computers, but are a key step toward programming complex biological circuits from scratch.”

Enlisting a patient’s immune in the battle against cancer growth has worked for specific types of the disease. In any case, focusing on strong tumors with this so-called CAR-T cell therapy approach has demonstrated challenging.

Scientists think part of the reason has to do with T cell exhaustion. Genetically altered T cells can fight for only so long before they stop working. There may be a way around this. With protein logic gates that respond to exhaustion signals, the team from UW Medicine hopes to prolong the activity of CAR T cells.

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

Journal Reference:
  1. De novo design of protein logic gates. DOI: 10.1126/science.aay2790

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