Introducing Core Biogenesis Platform for Ultra-scalable Bio-manufacturing

The last half-century of technological progress has been defined by the miniaturization of metallic components onto silicon wafers. The next century is being defined by our ability to engineer biology, or as Boston Consulting Group and Hello Tomorrow state, to “co-design with nature.”

Synthetic biology is one of the key enabling technologies that will drive a new green and sustainable economy that offers solutions such as:

  • plant and microbial biomass production,
  • bioenergy from (waste) biomass,
  • environmental protection and safety in terms of bioremediation,
  • green chemistry processes and applications,
  • sustainable agri-food production and processes, and
  • alternate food proteins, novel materials, and precision medicines.

The ability to easily engineer biology (“synthetic biology”) offers the opportunity to transform manufacturing from an industry that relies on unsustainable inputs to one that can produce almost everything sustainably and regeneratively. Synthetic biology comes at a time when the population is predicted to grow by another two billion people, when we need to increase the efficiencies of our agricultural systems, while at the same time considering the unanticipated effects of a changing climate.

The Molecules Limiting the Growth of Clean Meat and Cell Therapy

By leveraging the tools of synthetic biology, we can program microorganisms to manufacture almost any complex organic molecule, starting from scratch, building at the atomic level. Here are two examples:

The cell-based meat industry promises to revolutionize livestock agriculture by transforming protein production, something we need more of to feed our growing population. Known as “cultured meat,” “artificial meat,” “in-vitro meat,” and “cell-grown meat,” cell-based meat is meat that is obtained through in-vitro culture growth, rather than from growing and slaughtering animals.

According to the thinktank RethinkX, “the cost of [clean] proteins will be five times cheaper by 2030 and 10 times cheaper by 2035 than existing animal proteins, before ultimately approaching the cost of sugar.” The impact on industrial animal farming will be profound with the number of cows in the U.S. falling by more than 50 percent. Land freed from livestock and the agriculture necessary to feed that livestock could be used to grow food or regrow forests.

Cell-based meat production requires several growth media components, among them cellular growth factors that are required for the growth, maintenance, and differentiation of the cells that will become that delicious steak. Currently, those growth factors are derived from animals, which defeats the purpose of growing cell-based meat. Growth factors are also expensive. As a result, the manufacture of growth factors limits the growth of the cell-based meat industry.

Separately, cell therapy aims to introduce new, healthy cells into a patient’s body, to replace the diseased or missing ones. Potential applications of cell therapies include treating cancers, autoimmune disease, and infectious disease, rebuilding damaged cartilage in joints, repairing spinal cord injuries, improving a weakened immune system, and assisting patients with neurological disorders. Cell therapy candidates are in the clinic and progressing towards commercial approvals at an accelerated pace.

The promise of cell and gene therapy continues to expand, with the number of clinical trials rising by 14 percent in 2020 alone, and the market is expected to grow from US$9.5 billion in 2021 to US$23 billion in 2028.

Thanks to advances in cell biology and synthetic biology, we can grow customized cells in the lab that serve different therapeutic needs. But to grow the customized cells, the cell cultures need specialized growth media and, you guessed it, growth factors that keep cells happy and growing. In soluble form, the stability and bioactivity of growth factors decreases. They must then be purified to good manufacturing (GMP) standards, which is expensive. As a result, drug developers face the challenges of meeting increases in demand while scaling production processes efficiently.

You may have noticed that growth factors are limiting the growth (no pun intended) of both the cell-based meat and cell therapy industries. But this blog post isn’t about growth factors — it’s about the challenge faced by manufacturers producing valuable recombinant molecules at scale.

Ploughing with a yoke of horned cattle in Ancient Egypt. Painting from the burial chamber of Sennedjem, c. 1200 BC.

Humans Have Already Scaled Biomanufacturing

About 12,000 years ago, humans switched from being nomadic hunter-gatherers to permanent settlers and farmers. The development of agriculture — the first agricultural revolution — marks the dawn of civilization.

Humans have gone from learning how to domesticate plants to being able to manipulate them genetically. Selective breeding gave us modern crop plants. Phenotype screening allowed breeders to select and pinpoint specific crop traits. And now, in the era of engineered biology, we can work with plants to produce new biomolecules at scale.

Plants can be relatively easy to grow; genomes are well-known, well-studied, and some plants have very fast growth cycles, and if done correctly, some plants can compartmentalize recombinant molecules, enabling their rapid extraction potentially saving purification steps

Until now, the potential for using plants as biofactories has not been harnessed because of low expression yields and challenges associated with the extraction and purification of the recombinant molecules. The ability to engineer plants to produce recombinant molecules at scale could be a game-changer.

The Biggest Opportunity in Synthetic Biology

The synthetic biology industry’s growth is being driven by the creation of a stack of new technologies that enables and accelerates innovation through specialization.

The synbio technology stack includes:

  • The Application Layer, which includes products that are ready to be distributed or incorporated into consumer products and chemicals, proteins and complex systems ready for processing for end-consumer uses (e.g., leather, vanillin extract, growth factors).
  • The Component Layer, which includes biological parts or finalized biosystems that are commercializable, as well as materials, drugs, and industrial chemicals (e.g., chassis, bioparts, cells and pathways).
  • The Middleware Layer, which consists of a combination of hardware, software and biological applications (cloud labs, organisms test platforms) organisms engineering platforms and enabling infrastructure, technologies that help enable synbio applications.
  • The Infrastructure Layer, which includes both software and hardware solutions such as design and lab project management tools and robotics and liquid handling systems.

In December 2020, Judy Savitskaya and Vijay Pande from A16Z pointed out that

“Synthetic biology presents the tantalizing opportunity for scientists and entrepreneurs to choose from a menu of products and a menu of production processes independently, so neither decision constrains the other. Expanding the [production process or enabling infrastructure] menu represents a huge opportunity to make bio-manufactured products cheaper and thus far more likely to succeed in the market.”

Savitskaya and Pande noted that “Better production processes would help make the bioeconomy truly economical.”

In other words, expanding the Middleware Layer of the synthetic biology stack will expand synbio applications, helping increase yields while driving down costs.

As the synthetic biology ecosystem emerges, multiple value chains are being established and the manufacture of biomolecules will become an area of specialization and focus, offering scientists and entrepreneurs multiple ways to scale the production of their recombinant molecules.

In other words, the bioeconomy will be driven by multiple production processes.

Introducing Ultra-scalable Biomanufacturing as a Service (UBaaS)

Core Biogenesis has developed a proprietary platform that can massively increase production yields of recombinant proteins and massively increase extraction efficiencies.

We Call It Ultra-scalable Bioproduction-as-a-Service (UBaaS).

Our biofactory is a plant called Camelina sativa, a well-characterized, easy-to-grow plant that is native to Europe and Central Asia and has been cultivated as a crop for at least 3,000 years. Camelina sativa is also a very close relative of Arabidopsis thaliana, a plant widely used as a model species in research labs.

Camelina possesses a number of excellent agronomic traits:

  • It requires little water and fertilizer,
  • It is strongly resistant to insects,
  • Its genome is well characterized.

Based on ten years of research in plant genetics, epigenetics, and plant defense mechanisms, Core Biogenesis has developed a proprietary methodology to increase the yields of target recombinant molecules by using Camelina’s own genetic machinery.

We’re currently proving this technology with growth factors. In our initial tests, we scaled growth factors production more than 20x, while driving down costs by several orders of magnitude. We’ve initiated discussions with the world’s leading cell-based meat companies, and we have signed a deal with a biopharmaceutical company interested in our production technology.

As we think ahead replacing petroleum-derived products and mass-producing the enzymes that degrade plastics, are used for food processing, or even to manufacture DNA and RNAs, we foresee limitless applications of our technology.

We believe our UBaaS platform will become an essential part of building the bioeconomy. We look forward to keeping you updated on our progress at Core Biogenesis.

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