The Inscripta Blog

October 8, 2020
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Under the Hood: How Digital Genome Engineering Works

In October 2019, we launched the Onyx™ Digital Genome Engineering platform, the world’s first fully automated benchtop instrument for genome-scale engineering. The CRISPR-mediated, massively parallel platform includes software, consumables, instrument, and assays.

But if you’re a scientist, you want more than our description — you want to get under the hood. How does our technology work?

The Onyx platform is based on novel chemistry consisting of a guide RNA, which targets a region of the genome, and a homology sequence, which contains the desired edit for placement into the genome, linked together covalently for cell delivery. This linkage ensures that cells receive both important elements simultaneously, increasing the editing efficiency substantially. The covalent linkage of the guide RNA and the homology arm dramatically increases throughput, allowing scientists to target many locations throughout the genome with precise control in a uniquely scalable manner. The chemistry was originally developed by our founders at the University of Colorado, Boulder.

We also rely on innovations in partitioning that allow us to conduct CRISPR experiments within cells, giving our platform massive multiplexing capabilities. This allows scientists to make tens to thousands of edits in one run of the instrument, increasing not only the number but also the diversity of edits that can be produced in a single experiment.

The Onyx platform was designed to allow genome-scale engineering with as many edit types as possible, including promoter swaps or ladders, insertions, deletions, terminators, knock-outs, and more. Scientists can edit specific targets or take an unbiased, genome-wide approach. At launch, the platform can process edits as large as 60 base pairs and as many as 10,000 edits per library.

The workflow for our platform was designed to be as simple as possible. Scientists select their host strain and use our design software to create edits for all desired targets. They then order reagents directly through the user portal and get them in about 3 weeks. Loading the Onyx instrument is a piece of cake, and the rest of the experiment takes place inside. After a few days, the customer gets a tube containing the edited cell library and can begin screening that library for results of interest.

If you have ever used — or attempted to use — a CRISPR workflow, then you know how transformative it is to convert those tedious, temperamental methods into a push-button process. That’s why we’re so excited about our platform and its ability to let researchers focus on the science rather than the technique.

To learn more, check out the presentations given by Nandini Krishnamurthy and Richard Fox at SynBioBeta 2019.