Inscripta: The Future of Gene Editing

Aditya Mittal
5 min readSep 29, 2021

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As a company that recognizes that genes have already been read, Inscripta is blazing the way for the future by trying to write them through gene editing. Inscripta as a company is trying to make the first automated technology that is able to streamline the process of gene editing by CRISPR, which normally is a long, laborious process.

Through the Onyx platform, this process is simplified for scientists and allows them to look at genotype and variant analysis, while easily taking a deeper dive into the genomics they are researching. The program has the following:

  • Immense scale: It’s able to run parallel libraries quickly, power diverse edits (insertions, deletions, substitutions, mutations), and accelerate analysis. Compared to other competitors, it is able to use 1.5x less CPU power but run in 2x less time.
  • Greater audience: It’s able to reach a larger community since gene editing expertise is not required for running the application. Due to the technicality of gene editing, it’s inaccessible to many outside a scientific community, but Inscripta’s platform will allow anyone prototyping gene editing to be able to streamline their analysis without much prior knowledge.

Current Products

Onyx Instrument

This instrument automates many of the parallel genome engineering experiments, including CRISPR gene editing, cell growth, and cell recovery, with results available within a couple of days.

Due to its automatic pipeline, by simply installing the reagents, you will be able to run tens of analyses and monitor how it runs from the portal. It contains five microfluidic devices for these purposes:

  • Cell Growth Cuvette: managing/measuring optimal cell growth; Cuvettes are simply containers with straight sides and a square/circular cross-section on the bottom. They are used for holding samples for analysis, and Onyx’s cell growth cuvette is specialized in monitoring cells participating in cell growth.
  • Microfluidic Cell Controller: preparing cells for electroporation; Microfluidics is used to more accurately represent a cell’s environment and control the cell during growth.
  • Microfluidic Cell Transformer: performs electroporation; Electroporation is able to convert animal and plants cells by applying an electric field and introducing genes into the organism.
  • Cell Recovery Cuvette: managing cell growth during recovery; Similar to cell growth cuvettes, they monitor the cell as it “recovers” from the electroporation process.
  • Digital Engineering Processor: normalizing cell editing and growth; This process reviews DNA changes and normalizes them to reduce further growth of the cell outside of the control period.

Onyx Gene Editing Kits

These are customized to allow for the precise editing of the genome and accurately tracking the entire cell population through the use of nearly 10,000 Design DNAs.

Normally, in CRISPR, only one edit is performed per well, but by linking gRNA with the donor template, now over 10,000 edits can be multiplexed in a single tube with one ready-to-use cartridge per experiment.

Onyx Genotyping Assays

There are three major assays used by Onyx:

  • Control Edit Assay: a Sanger sequencing experiment that detects the absence or presence of internal control edits
  • Onyx Barcode Diversity Assay: a library preparation kit for NGS using Illumina — allows for the derivation of distribution of edits
  • Onyx Edit Identification Assay: library preparation kit for WGS using Illumina — can be run with isolates or pooled samples

Onyx Engineering Portal

This platform allows for the expediting of the genetic engineering process, due to its cloud-based system that allows for the design of thousands of genomic edits with maximal speed and efficiency. In addition to making the edits, there is the option to also review them with regards to their genomic context.

BioCantor

BioCantor is one of the tools that Inscripta has offered through a Python library; it allows for efficient transformations of arbitrarily related coordinate systems and analysis of genomic features.

It allows for the following features:

  • “Genomic feature arithmetic” — allowing for coordinate conversion of various features, binary and unary set operations across arbitrary coordinate systems
  • Abstraction — abstracts the process of converting genomic coordinate systems from the user
  • File format conversion — importing and exported known file formats.

Process

The basis of the BioCantor paradigm is that objects are defined by parent/child relationships. Once this hierarchy has been created, then coordinate operations can move around this hierarchy such converting feature annotations.

Example of usage of objects for referring to a parent sequence.

There are three main object types:

  • Location — represents blocked and stranded features represented by zero-based end coordinates; It has three implementations: EmptyLocation, SingleInterval (continuous interval), and CompoundInterval
  • Sequence — holds sequence data
  • Parent — defines parent/child relationships

BioCantor’s input files are normally GFF, FASTA, and GenBank files and are then parsed by BioCantor into GenBank, GFF3, NCBI TBL, and BED. Note that intermediate steps can be serialized to disk in JSON format.

JSON form of intermediate gene model step.

How Is Inscripta Pushing the Status Quo?

Inscripta is using and iterating on past algorithms and ideas to make the gene engineering process as streamlined as possible. For instance, BioCantor’s purpose was to iterate on past algorithms that weren’t able to easy convert between gene coordinate systems, such as Bedtools, BEDOPS, Pybedtools, and PyRanges.

With Inscripta, companies no longer have to spend thousands of dollars and hundreds of hours on analyzing gene editing data and can run a fully automated setup available through Onyx. This will allow for further advancements in gene editing, so scientists are able to free more time for experimentation rather than data analysis.

As seen above, Inscripta is doing some incredible things in the gene engineering space and will likely continue to do so in the future, revolutionizing the future. I’m excited to see what Inscripta does next, and how it will push the frontier of gene editing further.

If you want to talk more, schedule a meeting: Calendly! If you’re interested in connecting, follow me on Linkedin, Github, and Medium.

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