CRISPR-Chip Moves One Step Closer to the Genomics Market

Cardea Bio and Nanosens Innovations have announced today that they will be joining forces. By combining Nanosens’ CRISPR-Cas9 nucleotide detecting technology and Cardea’s graphene biosensor platform, to create a "CRISPR-Chip", they plan on providing the genomics and DNA detection industry with a product, lauded by some, as offering disruptive potential. 

We recently spoke with Michael Heltzen, Cardea Bio CEO (and Nanosens co-founder) to learn more about the merger. Heltzen shares insight into the development of the CRISPR-Chip technology and how it can be used to detect target sequences within intact genomic material. 

Molly Campbell (MC): Can you tell us about the merging of Nanosens Innovations Inc. and Cardea Bio Inc. – what expertise are you bringing together and why?

Michael Heltzen (MH): Cardea’s claim to fame is being the first and only company in the world able to mass produce graphene biosensors on a commercial scale.

The nanomaterial graphene can, like silicon, be used to build electronic transistors like those inside all the computer chips running smartphones and computers. Graphene has the extra unique property of being biocompatible – meaning that the “on” and “off” stage of the transistor gate can be “on” if a biological signal is present, and "off" if not. This is a novel way of making a direct connection between the complex but precise molecular signals involved in biology with a computers logical calculation abilities.

Biology works via many different kinds of molecular signals. For example, an antibody and an antigen, when bound, trigger a cascade of physiological mechanisms. Cardea's technology infrastructure allows researchers to see this happening by placing part of the binding interaction on the graphene transistor. Connecting the natural signals in biology with the calculation powers of computers opens up a brand new world of opportunities. Nanosens was the first start-up to deeply understand this opportunity that Cardea had created for protein-based signals. They asked: “What if we could also gain insight into DNA and RNA signals at the same time?”

A device that can measure both DNA, RNA and protein molecules in the same sample, at the same time, at near real-time and in a portable way would be the holy grail of life science insights. Other than in science fiction, no one has ever come close to creating this kind of technology.

2019 is the year when this "science fiction" dream starts to becomes a very obtainable technology. The collaborative efforts of Cardea and Nanosens have created the CRISPR-chip technology for instant DNA and RNA search, and it works with the protein detection that Cardea has developed. The union of these two companies presents an opportunity to unlock the ongoing biological R&D project that we call evolution.

MC: In June, you published a paper describing the development and testing of a graphene-based field-effect transistor that uses CRISPR technology to enable the digital detection of a target sequence within intact genomic material. Can you tell us more about the background of this research and the development of the chip? How exactly does it work?

MH: The CRISPR-Chip technology became the cover story of Nature Biomedical Engineering, and our peer-reviewed article quickly became the most read article.

Nanosens's co-founder Dr Kiana Aran had the innovative idea. She took the Cardea graphene biosensor and explored whether the CRISPR-Cas9 protein complex could sit on the sensor – allowing her to observe CRISPR in real-time through the computer screen.

Whilst everybody was talking about CRISPR as a gene-editing tool, Aran saw its core power as being able to search through genomes – looking for its target gene to cut – at great speed and with great precision. She utilized this genome search power by removing the gene-editing functionality (creating dead Cas9, or "dCas9) and put the CRISPR complex on the graphene biosensor chip.

Now, the "on" vs. "off" transistor was based on whether the CRISPR complex has successfully identified the target gene that you have asked it to look for (using the guide RNA "search query" functionality).

Aran soon realized that, in order to get accurate readings, she required a highly conductive material – the graphene sensor. Therefore, she reached out to Cardea. Cardea loved the innovative idea of a "DNA search engine". It resonates with Cardea's core mission to provide researchers with the tools and infrastructure to build the "Internet of Biology", where everyone can have fast and cheap insights into the biology that creates and surrounds us.

MC: How does the CRISPR-Chip expand the applications of CRISPR-dCas9 technology?

MH: CRISPR-Chip technology combined with Cas9 and dCas9 allows researchers to directly observe what CRISPR is doing in real-time, for the first time.

One application of this is to watch as CRISPR rapidly searches through genomes to identify mutations of interest; avoiding the amplification and optical detection workflows that current approaches require. This application will soon be launch as a produce called the Genome Sensor.

Another application is to provides a platform for researchers working with CRISPR as a gene-editing tool to "quality control" their gene edits, ensuring that they can avoid off target effects and achieve high precision in their gene-editing endeavors.

MC: How will the merging of Nanosens and Cardea facilitate further developments of this technology?

MH: Bringing the two companies together has already and will accelerate the innovation and novel ideas and R&D projects, taking full positive advantage of the how we as the first team can combine biology's naturally occurring functional processes directly with computer technology.

This new biology+technology infrastructure has already presented several new product opportunities across an array of applications and markets, so we are working with external partners on pursuing those opportunities. This is via what we call the “Powered by Cardea” Innovation Partnership Program. The Cardea and Nanosens collaboration is the result of five years of hard work, combining world class science with the best in class production of graphene sensors, and we will continue to innovate faster and faster. Via partnerships, we get to bring our technology to markets where we otherwise would not have access.

MC: What applications do you envision the CRISPR-Chip having in the short-term and the long-term?

MH: Right now we are deep into the first round of product development and early product launch phase, while keeping our fundamental R&D running at full speed. This is how we can utilize CRISPR-Chip tech to build the first standalone product and have equally exciting new technology and features coming in the soon future. The first commercially available product is going to be called the Genome Sensor and will allow the user to “DNA search genomes”. We will permit select individuals to use the Genome Sensor via our Early Access Program (EAP). This will help us better understand what researchers will want to use it for and will enable troubleshooting.

With the EAP, we expect to learn much more about how we can maximize the unique benefits of graphene biosensing, first with the CRISPR-chip technology being used in a few single analyte measurement projects and then we will start multiplexing and then combine the biosensor capability to sensor both DNA, RNA and Proteins, but it will take a bit of engineering to package it all on one chip. In the medium to long term, we want to apply the technology in genomics, transcriptomics and proteomics analytes and anywhere relevant in life sciences and people’s everyday life.

Michael Heltzen was speaking with Molly Campbell, Science Writer for Technology Networks.