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CRISPR is stuck, and this company can fix it

CRISPR may be the defining technology of this young century, but its arrival is also a kind of déjà vu on scale of the Human Genome Project. Back in 2003, we celebrated the $3 billion sequencing of a single human genome, though we scarcely understood what all those base pairs meant or what to do about them. Fast forward to today: CRISPR can theoretically let us remix entire genomes. But instead of true forward cell engineering, we’re still tinkering with one gene here, one gene there. Why? 

“Biologists, specifically genome engineers, are slowly trying to figure out what genome alterations generate the specific phenotype their application needs,” says Inscripta CEO Kevin Ness. He attributes this difficult process to two things: access to, and performance of, existing genome editing tools. “We haven’t had the ability to multiplex gene editing at a cost structure to allow you to truly operationalize biology.”

Kevin Ness

“Once scientists have access to the tools and technology that they need, the pace and volume of genetic research will accelerate toward the advancements that will truly help humanity“, said Inscripta CEO Kevin Ness in a recent Op/ed for GEN.

CRISPR-Cas9 is the most popular version of the gene editing enzyme and is freely available for academic research purposes only, which is great for deepening our scientific understanding of how biology works. But for projects with any commercial potential to break out of the lab, many startups, academic labs, and investors shy away from CRISPR-Cas9 because of prohibitive licensing and royalty costs.

“There are a lot of good projects and ideas standing on the sidelines because of these commercial access limitations,” Ness says.

To help solve the problem, a year ago Inscripta made MAD7, its proprietary CRISPR enzyme, freely available for research and commercial purposes. Ness claims it has been widely adopted in many diverse sectors, including energy, therapeutics, and food.

“We want to be good stewards of the bioeconomy by removing barriers to these important CRISPR nucleases, and MAD7 does this” says Ness. In doing so, the company is also growing its market. “We are enabling commercial gene editors,” he says, and with them more customers.

Earlier this year, Inscripta released data showing the potential for using MAD7 in human therapeutic and diagnostic applications, as well as biological development and manufacturing in a wide array of cell lines. The MAD7 DNA sequence has been downloaded more than 1,000 times in the last year and was recently named a Top 10 Innovation of 2018 by The Scientist.

Inscripta also announced that its investors were doubling down on the unusual strategy of giving away its CRISPR enzyme with another $30 million Round C extension, bringing their 2018 investment to $85 million. The latest round is intended to accelerate the development of an integrated technology suite of instrumentation, software, and reagents to enable forward cell-engineering “in a way never before possible.”

Among Inscripta’s investors is Venrock, the technology investment firm that helped start little companies like Apple, Intel, and Illumina. Inscripta’s investment and R&D team also includes many former Illumina and 10x Genomics executives, suggesting that they know something about how to build disruptive hardware platforms.

Inscripta is developing additional MADzymes, including bespoke enzymes for researchers and commercial partners. These nucleases are being engineered to have improved features such as different PAM recognition sequences, different cut efficiencies, reduced sizes, and different enzyme kinetics.

But the enzyme is just one part of the platform Inscripta is working on, and Ness has a big vision for Inscripta’s MAD7-based platform. He says the full suite of gene-editing tools (software, instruments, and reagents) will significantly increase the speed and efficiency of gene editing. “When you have complete knock-out and knock-in ability across the entire genome, coupled with the ability to rationally design and track cell variants in high multiplex and throughput” he says, “you can empirically find your genetic design winners with certainty.” Only then, he says, can you do true forward cell engineering.

“What Illumina did for genome reading, Inscripta is doing for genome writing ,” says Ness.

Kevin Costa

Kevin Costa

As Editor and Program Manager, Kevin leads SynBioBeta's digital media content and works with customers and partners to build a world-class community of innovators. Before joining SynBioBeta, Kevin managed the Synthetic Biology Engineering Research Center. His interests include public engagement, science writing, community building, and bikes!

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