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GENOMEWEB Interview of Ross Bundy, CRISPR QC CEO

With $1.6 million of seed funding recently added to its balance sheet, CRISPR QC is advancing the commercial development of its data analytics platform for gene editing.

The San Diego-based startup currently offers an in vitro CRISPR-based assay as a service to help customers gain insights into the performance of their gene editing experiments — such as guide RNA (gRNA) interaction, target recognition, and cleavage. It also hopes to develop its technology into a standardized QC platform that can be deployed in labs to help researchers optimize their experiments.

According to President Ross Bundy, the core of the company’s platform is a technology called CRISPR-Chip, a CRISPR-Cas9-based biosensor invented by company Cofounder Kiana Aran that is capable of directly measuring CRISPR activity.

Initially described in a Nature Biomedical Engineering paper in 2019, the CRISPR-Chip technology combines the gene-targeting ability of deactivated Cas9 complexed with a specific guide RNA with a graphene field-effect transistor to detect DNA targets without the need for amplification, labeling, or optical instruments.

“The technology allows us to interrogate biochemistry with some of the much more complex analysis you get from the semiconductor industry,” said Bundy. “As a result, we can actually see the activity of how the molecules operate on the DNA.”

Before launching CRISPR QC in late 2021, Bundy had served as the founding CEO of Cardea Bio, a company also based in San Diego that has been commercializing the CRISPR-Chip technology into mass-produced Biosignal Processing Unit (BPU) chips. Bundy said CRISPR QC has obtained an exclusive license from Cardea Bio in the gene-editing space to develop CRISPR-Chip into products that can measure CRISPR-Cas performance.

Mechanistically, CRISPR-Chip utilizes a graphene surface functionalized with pyrenebutyric acid (PBA), which can electrostatically interact with the graphene and be linked to any Cas protein, according to CRISPR QC’s website.

As molecules bind near the graphene surface, the current changes between the drain and source electrodes, generating a signal that deviates from the baseline. Additional reagents, such as PCR-amplified target DNA or reaction components, can also be added to measure binding interactions or cleavage reactions.

“The benefit of our technology is that the sensors are all electronic — there's no optics, no microfluidics,” Bundy pointed out, adding that another advantage of the electronic sensor is that it can be deployed in parallel in order to generate multiple measurements at once.

While the CRISPR-Chip technology is chemistry agnostic, the BPU chips are currently designed to measure a single condition at a time, Bundy said. However, he said it is “entirely feasible to boost the multiplexing capability” of the chip.

Currently, CRISPR QC offers CRISPR-Chip technology to customers as a service, which is carried out in a fully automated workflow. In terms of the hardware, he noted that despite the company’s current platform being custom-made, “every one of those pieces is commercial off-the-shelf electronics.”

Depending on the analyte, Bundy said, the assay can take between two and seven hours to complete, plus a few more hours for reagent preparation. He noted that data analysis is currently the “slowest point” of the technology’s workflow, and the company is trying to scale up the analytics to make the data coming off the sensor easier to interpret.

Application-wise, Bundy said the company’s technology can be beneficial to a multitude of ventures that involve gene editing, from developing climate-resistant crops to targeted gene therapy for rare diseases.

“What's great about gene editing and CRISPR is that you have a single vertical of chemistry, but the applications go very wide,” he said, adding that CRISPR QC is already working with several companies in the agriculture and gene therapy sectors. In addition, Bundy said the company is currently talking with contract development and manufacturing companies in the pharmaceutical industry.

Elaborating on the company’s relationship with Cardea Bio, Bundy said that while Cardea Bio supplies the BPU chips to the firm, it is “a very horizontal company” that does not intend to delve deep into specific applications of the CRISPR-Chip technology.

“Think of Cardea like Intel,” he explained. “You have probably never bought a chip from Intel, but you own products that exist because of Intel.” Additionally, he said Cardea Bio plays the role of an arbitrator when licensing out its IP for different applications to ensure that its downstream partners “stay in [their] swimming lanes” while allowing room for them to collaborate and add value to each other.

To that end, while CRISPR-Chip can be tapped for other applications, such as biosensor-based disease detection, Bundy said CRISPR-QC’s interest is solely in the gene-editing space.

CRISPR QC will use its seed funding to continue advancing its technology and commercial pipeline. To do that, Bundy said the firm plans to keep driving customer awareness of the CRISPR-Chip platform and educate them on the technology’s potential capabilities. The firm is also working with collaborators from the government and commercial sectors to publish a paper that correlates CRISPR QC data with gene-editing performance and cell outcomes.

The company, which currently has six employees, also plans to expand its workforce. “My goal is by the end of the year, we will have 20-plus people on the data side, the commercial side, and scaling up our labs,” Bundy said.

While CRISPR QC only offers its technology as a service at the moment, in the long run, it hopes to transform CRISPR-Chip into a piece of standard lab equipment — like Thermo Fisher Scientific’s NanoDrop spectrophotometer, for example — that can be deployed in labs to help scientists perform validation and quality control of their gene-editing experiments.

“That's where we want to be,” Bundy said. “We have a long way to get there, but the initial steps we're taking are already working in a very positive way.”

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