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Nucleic Acid Strands Show Basics Of Computing Operations Inside Mammalian Cells

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Thanks to nucleic acid strands, scientists have recently implemented basic computing procedures inside living mammalian cells.

This breakthrough is believed to help create an artificial sensing process that can potentially control cell behavior in case of a stimulus, such as a cancer or toxic invasion. For instance, it could serve as the basis for biocomputers to detect, analyze, and modify molecular details in cells.

Researchers used displacement of DNA strands – widely used in designing molecular circuits, sensors, and motors – and adjusted the process by incorporating “AND” and “OR” logic gates that capably work inside the cells and work with messenger RNA.

Philip Santangelo, study author and associate professor at Georgia Tech and Emory University, said they intended to use the logic employed in computers in the cell itself.

"These devices could sense an aberrant RNA, for instance, and then shut down cellular translation or induce cell death,” he explained in a press release.

This technology is the biological version of the gates or switches building the foundation of silicon-based computing. They can be activated to turn on or off when responding to external stimuli, including a single molecule. The “AND” gate switches when both preconditions are satisfied, while the “OR” gate activates when either is satisfied.

In this endeavor, the team used switches with a fluorophore reporter molecule as well as a complementary quenching molecule positioned to form an “off” setting. RNA binding in a strand afterwards displaced a nucleic acid portion to separate the molecules and then incite a signal creating an “on” mode. Forming an “AND” gate are two “on” modes situated on adjacent strands of the nucleic acid.

According to University of Washington assistant professor Georg Seelig, implementing specific logic gates marks only the beginning – they aim to widen the technology and create multi-input circuits including those built in non-cell environments.

Ligands bound specific nucleic acid strand parts, something that can be commercially produced.

The research was years in the making, as enabling basic computing systems to work inside cells comes with challenges – getting a device into a cell without triggering a switch and taking care not to kill the lab-setting human cells, to name a few.

The computers worked as designed, with the next move involving the ability to trigger the creation of signaling chemicals that will incite the intended cell reactions.

Protein production usually controls cellular activity, thus the switches should be allowed to create plenty of signaling molecules to introduce change and get a cell to react. That last step is yet to be done.

While cells are able to detect toxic molecules, such sensing capability can be maimed by cancer cells or viruses. “[We want to] give cells a hand at doing this,” added Santangelo.

The findings were published Dec. 21 in the journal Nature Nanotechnology.

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