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6 Protein Engineering Startups Designing Biology

It’s up for debate which human invention should be considered the greatest of all time. Some would argue the wheel. Others might say MTV (the 1980s version at least), while cases could also be made for everything from the printing press to the internal combustion engine. We vote for beer—but probably not for the reasons you would think. Sure, we love our hoppy IPAs for the brain damaging euphoric moments of enlightenment that it can bring. However, the ability of yeast to ferment sugars into alcohol has provided an essential model for the biotechnology industry of today. Protein engineering companies are designing unique molecules to develop a wide range of products, from scents and flavors to proteins that help crops grow faster or make veggie burgers bleed. Yeasts or other microorganisms are then genetically tweaked to help brew up the latest Flubber.

Protein engineering is a branch of biotechnology that falls under a discipline called synthetic biology. Synthetic biology approaches the natural world from an engineering perspective, imagining cells as machines that can be designed to do specific jobs. Automation through robotics and artificial intelligence or other sophisticated software is enabling companies to design billions of these “machines” rapidly to find the right molecule for the job.

Credit: SynBioBeta

The overall synthetic biology industry is also rapidly attracting venture capital dollars. The top 50 VC deals last year netted a record-high $1.7 billion in investments. The top-funded company in 2017 at $275 million was Ginkgo Bioworks, which jumped into the fantasyland of unicorns, private companies valued at over $1 billion. Ginkgo Bioworks is at the forefront of what the company calls organism engineering. But it’s far from alone.

Protein Engineering Blueprints

Founded in 2008, Seattle-based Arzeda took in a $15.2 million Series A last year, the first time the protein engineering startup has raised capital since an undisclosed Seed round way back in 2009, preferring to bootstrap the operation until recently. OS Fund led the first $12 million chunk in July. OS Fund was co-founded by Bryan Johnson—the brilliant entrepreneur (despite having the handicap of an MBA) of such hits as Braintree and Kernel—and has invested in startups such as the aforementioned Ginkgo Bioworks, as well as Hampton Creek, Planetary Resources and uBiome, among others. In addition, Arzeda spun out of the University of Washington’s Institute for Protein Design, where co-founder David Baker is the director and one of the pioneers in working with protein structures. In other words, Arzeda has serious street cred.

The company designs enzymes—proteins that are responsible for complex actions throughout nature—for both agricultural and manufacturing purposes. One of its key customers is DuPont Pioneer, which uses the novel proteins to help make crop seeds such as corn grow like gangbusters. Arzeda is also developing new-to-nature enzymes that can synthetically produce butadiene, a molecule normally sourced from petroleum but a key ingredient in products such as nylon, paints and even rocket fuel.

Examples of Arzeda’s cell factories. Credit: Arzeda

Arzeda mainly focuses on protein engineering, basically developing the “blueprint” needed to create the DNA sequences necessary to code for the new proteins. The industrial production of the desired molecules is done by Arzeda’s customers or contract manufacturers, which genetically modify yeast or other microbes to go to work in fermentation vats—just like brewing beer, but without the hangover.

Protein Engineering Software

Apparently Baker is not just a brilliant scientist but something of a serial entrepreneur himself. Founded in 2014, Seattle-based Cyrus Biotechnology has raised $10.4 million, with $9 million coming in two separate rounds in the big synbio year of 2017. The company has commercialized a protein-design software called Rosetta that was developed in Baker’s lab at the University of Washington. The cloud-based platform is called CyrusBench, named after Cyrus Levinthal who back in 1969 (presumably dosed on LSD) said it would be impossible to predict the many ways a protein could fold. As you may recall from that brilliant biochemistry course you took in high school from that obese, sweaty football coach, proteins are made up of a chain of amino acids that fold in nearly infinite ways. The structure of the protein is what defines its function, such as breaking down alcohol or carrying oxygen in blood to the few remaining brain cells from said alcohol.

CryusBench: CAD for protein engineering. Credit: Cyrus Biotechnology

CyrusBench is intended to help democratize protein design for the average biotech scientist. The software is being applied to help find molecules that could treat brain cancer, break down gluten in Celiac disease patients and block various flu strains. One customer, for instance, used the software to tweak the binding characteristics of a commercially important enzyme. Using CyrusBench, the biotech client not only saved months of labor but avoided millions of dollars in additional expenses to produce the desired effect. And there is also a protein-folding game for citizen scientists.

Protein Engineering for Celiac Disease

Why stop at two companies? Baker is also a co-founder and advisory board member for San Diego-based PvP Biologics, which got $35 million from Takeda Pharmaceutical, one of the largest drug makers in the world. Another University of Washington spinoff founded in 2016, PvP Biologics is trying to develop a very specific protein therapy to tackle Celiac disease, a condition that affects about 1 percent of the population but has led 99 percent of us to becoming increasingly annoyed with seeing labels like gluten-free coffee or gluten-free shoe wax.

An artistic rendering of KumaMax. Credit: Vikram Mulligan at Baker Lab

The protein engineering startup is developing KumaMax, a novel enzyme that can survive the harsh conditions of the stomach in order to target the parts of gluten that trigger the autoimmune reaction that leads to celiac disease, which can damage the small intestine. One day we hope to see a cure for gluten-free bakeries.

Protein Engineering for the Flu

Why, no, Dr. Baker is not yet done. Meet Virvio, yet another UW spinoff that was founded in 2015 in Seattle. Funding for the company only lists a $200,000 grant from the National Institutes of Health. Virvio thinks antibodies are so 20th century; the company is engineering novel proteins to tackle conditions as diverse as asthma and the flu. Remember how we said the world would be a better place if scientists could create a universal flu vaccine? That’s certainly on the list at Virvio, which has created a anti-flu mini-binder that attaches to the surface of the virus, preventing it from doing any damage.

Can’t get enough of Dr. Baker? Check out this article about his work on the New York Times or this one on Science News.

Protein Engineering with AI

Founded in 2012, London-based LabGenius has nothing to do with Baker as far as we know. The company, which took in $3.7 million in a Seed round last year, is more in the mold of a startup like Zymergen. It employs artificial intelligence and robotics to develop novel proteins to create new materials such as adhesives and even for anti-wrinkle healthcare products. The protein engineering startup built an AI platform called EVA that designs, conducts and even learns from its own experiments. The machine learning part means that EVA gets continuously smarter as it “unpicks the genetic design rules” that underpin life.

Even More Protein Engineering

Finally, a synthetic biology company with a different twist on protein engineering. Founded in 2014, Synthorx out of California has raised $16 million. One of its founders, a chemist named Floyd Romesberg at Scripps Research Institute, did a little something a few years ago—adding two synthetic letters to the code of life. By adding the DNA letters X and Y, cells can make proteins with up to 172 different amino acids versus the 20 amino acids created by Mother Nature:

Credit: Synthorox

Based on that discovery, scientists might develop more powerful drugs without dangerous side effects, for example. One project hopes to turn spider venom into a non-addictive painkiller, according to an article in MIT Technology Review. The com­pany is also focused on protein therapies for cancer and au­toim­mune dis­eases. If you want to read more about the company, check out our article on how Synthorx Takes Synthetic Life to a Whole New Level.

Conclusion

We’ve been preaching about the possibilities around synthetic biology for about five years now, but have tempered our enthusiasm with the economic realities that many of the public companies are not doing so hot on the stock market. For example, we were quite excited about a company called Intrexon (NYSE:XON) that we learned about around that time. The company even acquired a protein therapeutics startup about three years ago, and the stock was performing quite well making us think that just maybe, XON was the synthetic biology darling we’d been waiting for. Today, XON is down -38% since their IPO and we’ve highlighted some serious concerns about their progress so far. As we’ve learned over the years with carbon nanotubes and graphene, exciting technologies don’t always present good investment opportunities for retail investors.

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