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The EntoEngine

See how the EntoEngine can express your protein

Fruit flies for advanced biomanufacturing

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Reinventing recombinant protein production.

Using Drosophila melanogaster as the expression host, our first-of-its-kind EntoEngine™ combines genetic engineering with insect farming to produce recombinant proteins at scale.

Drosophila melanogaster


Key Advantages

Multicellular Expression

200+ distinct cell types with the genetic tools to selectively target expression–all in one platform

Inducible Expression

Robust, efficient, and pharma-safe inducible expression at scale, unlocking toxic protein production

Unparalleled Scaling Potential

Cost-effective and flexible, offering custom batch sizes from micrograms to grams

Genetic Stability

Long-term stability of expression strains means clients can receive quality proteins on-demand

Why flies?

E. coli and yeast offer speed and flexibility, but lack robust scale-up production capabilities.

This creates the need for stable cells lines, which results in a significant timeline bottleneck.

The EntoEngine eliminates trade-offs and bottlenecks with stable protein expression for large-scale commercial manufacturing.

The Question
How to scale up with affordability and efficiency?

The Problem
Bioreactor-based
Expression method

The Solution
EntoEngine™
Expression method

Scaling up in bioreactors requires constant, expensive optimization and compromise.
Scaling up with the EntoEngine™ is modular and fast, producing micrograms to grams of recombinant protein daily.

The Question
How to scale up with affordability and efficiency?

The Problem
Bioreactor-based
Expression method

Scaling up in bioreactors requires constant, expensive optimization and compromise.

The Solution
EntoEngine™
Expression method

Scaling up with the EntoEngine™ is modular and fast, producing micrograms to grams of recombinant protein daily.

Production Process: EntoEngine™ in Action

Upstream
Downstream
Upstream
Downstream
    Ribbon diagram of a folded protein with alpha helices and beta sheets structures in red and pale green regions
    Protein target is selected
    Circular plasmid DNA illustration with the gene of interest highlighted in red.
    Plasmid is engineered to contain the gene of interest
    Automated microinjection system with a compact black and white housing.
    Engineered plasmid is microinjected into Drosophila embryos
    A western blot readout with distinct protein bands along with molecular weight ladder on a horizontal screen.
    Drosophila are bred to produce a balanced expression strain -> expression is tested and confirmed
    Fruit fly larval biomass represented by orange-brown color in a small vial, a glass jar, a tray, and a set of stacked trays on a large rack.
    Drosophila expressing the protein of interest are scaled up
    Two clear glass jars, one with orange-brown liquid (pre-centrifugation) and one containing a colorless clarified solution.
    Biomass is homogenized and resulting lysate is clarified via centrifuge
    Chromatography instrument connected to a computer monitor and control screen.
    Clarified lysate is loaded into chromatography systems for purification
    Row of multicolored 3D histogram next to a clipboard holding a checklist.
    Purified protein is tested for functionality, activity, and safety across lots
    Assorted labeled vials filled with finished products arranged together.
    Final deliverable passes quality controls and is shipped to client in desired form

    EntoEngine FAQ

    The EntoEngine employs Drosophila melanogaster (fruit flies) as a multi-cellular, whole-insect bioreactor to produce recombinant proteins. We genetically engineer transgenic flies with stable integration of the gene of interest into the genome. This is followed by protein expression, extraction, and purification. Click here to read more.

    Yes! Alongside difficult-to-express proteins, the EntoEngine can make simple proteins such as basic fibroblast growth factors. With the natural efficiency of Drosophila, the EntoEngine can produce high performing active proteins at competitive prices.

    Yes, we can. The co-expression of multiple proteins is a powerful approach often necessary for creating functional protein complexes. Our whole-insect expression approach is uniquely equipped to handle this process. For example, we successfully used our EntoEngine platform to express two different subunits that then assembled into a single, functional heterodimeric unit.

    The EntoEngine is a stable expression system. This is significantly faster than traditional expression systems because our approach does not require the production of a Master Cell Bank (MCB). The MCB process, which involves generating a homogenous cell population, can add to the project’s timeline. Our approach bypasses this step by directly creating stable transgenic flies, therefore accelerating the proof-of-concept phase.

    The EntoEngine platform offers a sustainable and versatile alternative to conventional systems like CHO and E. coli. While E. coli is cost-effective, it can struggle in the manufacturing of complex proteins with post-translational modifications (PTMs). CHO cells can handle complex proteins with PTMs, but they are often capital-intensive and time consuming at scale. The EntoEngine, by contrast, uses fruit flies as a bioreactor to efficiently produce complex and “difficult-to-express” proteins with PTMs. Our approach significantly reduces the capital costs, resource conception, and environmental footprint compared to the conventional methods.

    Read more on our blog article, “Overview of Recombinant Protein Expression Systems

    Our platform has demonstrated its ability to express functionally active recombinant proteins ranging from 4 kDa to 250 kDa in size, and we continue to expand this range.

    EntoEngine can produce glycosylated proteins without the immunogenic 𝛼1,3-Fucosylation, consistently and without batch-to-batch variations.

    Read our latest case study on insect glycosylation using Erythropoietin as a model protein.

    The EntoEngine’s yield is comparable to that of conventional CHO bioreactors on a time-normalized scale, a metric that accounts for the full production cycle. With our whole-insect bioreactor approach, the turnaround time becomes faster, making the EntoEngine a highly efficient and competitive platform.

    The EntoEngine is equipped with a cost-efficient, inducible expression approach.This method prevents unwanted constitutive expression, preserving production of the protein of interest regardless of host-cell toxicity.

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