The CRISPR gene-editing system is usually known for helping scientists treat genetic diseases, but the technology has a whole range of possible uses in synthetic biology too. Now researchers at ETH Zurich have used CRISPR to build functional biocomputers inside human cells.

As powerful as modern computers are, nature bested us long ago. Living organisms could be thought of as computers already – their cells act like logic gates, taking input from the outside world, processing it and responding with certain metabolic processes.

"The human body itself is a large computer," says Martin Fussenegger, lead researcher of the study. "Its metabolism has drawn on the computing power of trillions of cells since time immemorial. And in contrast to a technical supercomputer, this large computer needs just a slice of bread for energy."

Tapping into these natural processes to build logic circuits is a key goal of synthetic biology. In this case, the ETH Zurich team found a way to slot dual-core processors into human cells by first modifying the CRISPR gene-editing tool. Normally, this system uses guide RNA sequences to target specific DNA segments in the genome, then make precise edits. For this project though, the team created a special version of the Cas9 enzyme that can act as a processor.

This special Cas9 instead reads guide RNA as inputs, and in response expresses particular genes. That in turn creates certain proteins as the output. These processors act like digital half adders – essentially, they can compare two inputs or add two binary numbers, and deliver two outputs. To boost the computing power, the researchers managed to squeeze two processor cores into one cell.

In the long run, these dual-core cell computers could be stacked up by the billion to make powerful biocomputers for diagnosing and treating disease. For example, the team says they could look for biomarkers and respond by creating different therapeutic molecules, depending on whether one, the other or both biomarkers are present.

"Imagine a microtissue with billions of cells, each equipped with its own dual-core processor," says Fussenegger. "Such 'computational organs' could theoretically attain computing power that far outstrips that of a digital supercomputer – and using just a fraction of the energy."

The research was published in the journal PNAS.

Source: ETH Zurich