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CRISPR used to develop the first synthetic dual-core biocomputer.

In biology, cells sense and process many environmental inputs.  Hence, these inputs are then processed to produce outputs, such as development, differentiation, or immune responses modulated via the regulation of specific gene switches by intrinsically programmed gene circuits. 

Controlling gene expression through gene switches in synthetic biology historically uses logic gates to process input signals.  However, these circuits, usually built with the help of protein gene switches in cells, have met some serious disadvantages. 

Now, a study from researchers at ETH Zurich integrates two CRISPR-Cas9-based core processors into human cells.  The team states their processor is based on a modified CRISPR-Cas9 system which can work with as many inputs as desired in the form of RNA molecules.  The opensource study is published in the journal PNAS.

A programmable biocomputer

Previous studies have indicated the more complex computational processes in cells are only possible under certain conditions, making them unreliable and prone to failure.  In fact, even in the digital world, circuits depend on a single input in the form of electrons with electronic circuits compensating for this with their speed, executing up to a billion commands per second.

Comparatively, cells are slower, processing up to 100,000 different metabolic molecules per second as inputs. However,  this vast biological processing potential has yet to be fully realized.  The current study uses biological components to construct a flexible core processor via CRISPR, or central processing unit (CPU), which accepts different kinds of programming.

The current study utilizes a special variant of the CRISPR Cas9 protein to form the core of the processor. Results show in response to input delivered by guide RNA sequences, the CPU regulates the expression of a particular gene. This, in turn, produces a particular protein. Data findings show this biological CPU can program scalable circuits in human cells, consisting of two inputs and two outputs, and can add two single-digit binary numbers together.

RNA programs the biocomputer

The lab then developed a biological dual-core processor, similar to those in the digital world, by integrating two cores into a cell. To do so, they used CRISPR-Cas9 components from two different bacteria, developing the first cell computer with more than one core processor.  The team states their computational organs could theoretically attain a computing power much greater than the capacity of a digital supercomputer, using just a fraction of the energy.

The team surmises they have used CRISPR/Cas9 technology to develop a dual-core processor in a human cell. Additionally, this biocomputer can be programmed to perform complex operations with different sets of RNA inputs.  For the future, the researchers state a biocomputer could one day be used to detect biomarkers in the body, process them and respond to them accordingly, much like an intelligent drug.

Source: ETH Zurich

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