Biology has never been easier to engineer

What was previously done on a single-gene scale over a period of weeks and months can now be implemented on the level of pathways, networks, and whole genomes – in just a few days.

As biotechnology makes its way to the center stage as a prominent player in the 21st century economy, the demand for rapid engineering of biological systems is accelerating. The iterative Design-Generate-Test-Learn (DGTL) cycle — designing new DNA sequences, generating genomic edits, testing the edited organisms for desired functions, and learning from the genotype-phenotype relationships — drives the discovery process. This has catalyzed the emergence of technologies to facilitate the process of genome engineering.
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Creating tools to engineer biology

Filling the gap between the potential of biotechnology and existing genome engineering capabilities requires a novel approach to be able to engineer cells en masse, coupled with a feasible way to monitor phenotypic outcomes. The Inscripta® Onyx® solution uses the patented CRISPR-enabled trackable genome engineering (CREATE) technology [1]. The CREATE method relies on 3 essential components expressed from a single plasmid: the gRNA, the editing cassette, and a barcode sequence to identify the edit. The link between the genomic edit and the barcode allows identification of the engineered cells by simply sequencing the barcoded region of the plasmid and tracking of tens of thousands of edited cells within a population.

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Enabling scientists to achieve what was previously impossible

With Inscripta’s Onyx technology, CRISPR editing is finally realizing the potential envisioned by its developers. Onyx allows the introduction of a variety of edit types, from single-nucleotide substitutions to large insertions and deletions, with high efficiency and precision. Individual cells act as partitions in a massively parallel genome editing experiment, thanks to our advanced microfluidic technology. The diversity of genomic edits and ease of genotyping that Onyx enables facilitates scores of applications that range from proteins and pathways to genome-level engineering.
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Building an ecosystem

Onyx removes the technical barriers to implementing high-throughput genome editing so that you can focus on hypothesis generation and testing. It allows you to easily design large, complex, genome-wide libraries of various edit types with the click of a mouse, carries out all required cell manipulations inside of a benchtop instrument, ensures that the edits are incorporated at high rate, and tracks the edit distribution through the population.

Re-writing biological programs

Instead of editing individual genes, we now have the ability to re-write the entire software that encodes the execution of biological programs. This includes not just known genes, but the genomic regions that have not been functionally annotated yet (the Y‑ome), regulatory structures, non-coding regions, and more. The complexity of the genome yields itself to limitless exploration that probes how changes in these genetic elements influence the resulting phenotypes.
With Onyx, you can easily create a diverse variant library of cells and carry them forward to phenotyping, followed by subsequent rounds of editing.

Benefits

Cas nuclease
Versatile
  • Inscripta scientists and independent researchers have shown MAD7 effectively generates indels in a range of organisms: microbes, plants, mammalian cell lines, iPSCs, and animal models
  • MAD7’s thymidine-rich PAM recognition provides genome scale access for editing in diverse cell systems.
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Proven Performance
  • Type V nucleases such as MAD7, in general, have lower off-target effects as compared to type II nucleases
  • A single nuclease domain creates double stranded breaks with staggered overhangs that can aid in HDR mediated experiments
  • Smaller size and payload are optimal for viral and plasmid delivery methods
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Greater Access
  • Non-exclusive licenses are available for various research, development, and commercial applications
  • Hundreds of scientists in academia and industry have licensed & utilized MAD7 since its release in 2017
Learn more about how the Onyx platform can accelerate your research.
References
  • [1] Garst, Andrew D., et al. Genome-wide mapping of mutations at single-nucleotide resolution for protein, metabolic and genome engineering.” Nature biotechnology 35.1 (2017): 48 – 55.