CRISPR to electronically regulate genes
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CRISPR To Electronically Regulate Genes – Linking Electronics & Biology

University of Maryland (UMD) researchers developed a novel way to electronically turn genes “on” or “off” utilizing CRISPR technology, in an effort to create first-of-kind microelectronic devices that connect with biological systems.

The gap between the biological and electronic worlds could be further bridged by this new technique, published in Nature Communications. This new technology can pave the way for new smart and wearable devices.

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COVID-19 pandemic has shown us how ‘smart’ devices could benefit the general population. A wearable device that could detect if the wearer has been infected or not and if he has generated immunity would have reduced COVID-19 impacts a lot.

Such a device is not ready yet. But it is clear that the rapid transfer of information between electronics and biology is needed to make this a reality.

Microelectronics like implantable pacemakers and personal wearables have greatly evolved in the last few years. Devices first implantable pacemaker to personal wearables. Devices that can tap into and control molecules like hormones, DNA, or glucose to improve human health could be the next wave of microelectronics.

But, there is a major challenge for doing so. Todays’s advanced microelectronic devices use materials like gold, silicon, or chemicals to process information and an energy source that provides electrons. But biological systems do not contain free electrons. Therefore, a gap exists between the biological and microelectronic world.

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CRISPR to electronically regulate genes

However, William E. Bentley, a professor at UMD’s Fischell Department of Bioengineering and Institute for Bioscience and Biotechnology Research (IBBR), his colleague Gregory F, and their teams discovered a loophole over two years ago.

A small class of molecules capable of shuttling electrons already exists in biological systems. These molecules that can transport electrons to any location are called “redox” molecules. To transport electrons to the desired target, the redox molecules must first undergo a series of oxidation or reduction reactions.

Bentley’s research team created a sophisticated synthetic “switching” system in bacterial cells by engineering cells with synthetic biology components. The “switching” system incorporates the biologically programmable genetic circuitry of CRISPR and recognizes electrons instead of more traditional molecular signals.

CRISPR, a widely used tool for gene editing, was modified to work with a regulatory protein called SoxR in E.coli that is responsive to redox molecules. The research team used CRISPR to focus on a cell’s metabolic machinery to carry out desired functions, instead of using it for editing genes.

In E.coli as well as Salmonella, they used CRISPR to electrically program the upregulation and downregulation of specific genes. The same medium of redox was used as a communication channel to transmit electrically programmed information to and within many strains of bacteria.

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The team used electronic signals to create a chemical gradient of the CRISPR-controlling extracellular signals in immobilized cells in a gel. They showed that cells exposed to minimally oxidized pyocyanin (a metabolite capable of participating in a redox reaction) showcased the lowest level of CRISPR activity while cells exposed to the most highly oxidized pyocyanin demonstrated the highest level of CRISPR activity. Thus, they used electrical signals to spatially control CRISPR.

This is the first time CRISPR is being used to electronically target and regulate genes.