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Bringing Big SynBio to the Big City

New York City is not for everyone. It has a reputation for being crowded, expensive, and frenetic. But it is still, as one writer puts it, the City of…

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New York City is not for everyone. It has a reputation for being crowded, expensive, and frenetic. But it is still, as one writer puts it, the City of Ambition. Having attained preeminence in finance and publishing, NYC is now rising in biotech. Indeed, NYC is starting to vie with the traditional biotech hubs—Boston and San Francisco—for the favor of synthetic biology (synbio) companies, as evidenced by the growing number of synbio startups that have made the Big Apple their home.

The startups say that the real estate in NYC is surprisingly reasonable in comparison with that in Kendall Square or South San Francisco. The energy in NYC jives well with getting a startup off the ground, and the crowds bring with them large pools of talent.

On top of those reasons, NYC is where high-end products are made. With synbio poised to make inroads in industries such as fabrics and food, what better place to be than sandwiched between the top fashion houses and the best restaurants in the world? When more products from the laboratory start hitting the consumer market, New Yorkers will show that their trendsetting ways apply not only to cuisine, culture, and capital, but to synbio as well.

A palm oil alternative from microbes

Seldom do graduate courses offer life-changing experiences. But a course called “Revolutionary Ventures” at the MIT Media Lab did that for MBA student Shara Ticku. She found a new purpose not so much from the lectures she attended, but from the interactions she had with her classmates, especially Harry McNamara, PhD, and David Heller. The three had a mutual concern about the environment and, more specifically, the destruction of primary forest by palm oil production.

Palm oil is the most popular vegetable oil in the world. It’s found in 50% of products on supermarket shelves, and it was a $60 billion industry in 2016. It is “truly ubiquitous,” notes Ticku. “Every single person uses palm oil in some way, shape, or form every day, even if they try to avoid it. It’s just so widespread.”

Palm oil also the most destructive vegetable oil from a greenhouse gas and a social perspective.

Consumer-packaged-goods companies—250 of them—made public declarations several years ago that they were going to stop using conflict palm oil, which is associated with deforestation. But the companies subsequently struggled to fulfill their promises. Why? Because there is no viable alternative to palm oil.

Ticku, Heller, and McNamara had the idea to do something about the palm oil problem. They realized that where agriculture failed, synbio might succeed. To explore this possibility, they founded C16 Biosciences. From the start, the company was committed to using microbes to brew a sustainable alternative to palm oil.

C16 Biosciences, a synbio startup that develops sustainable alternatives to palm oil, is located in the Hudson Research Center (HRC) on Manhattan’s West Side—a “hub for innovation and collaboration.” Seven companies (or organizations) currently call the HRC home, including the New York Stem Cell Foundation. Although the building’s modern office and laboratory space would be attractive to any startup, the unparalleled views of the Hudson River offer a unique amenity.

After identifying a yeast strain that produces oil like palm oil, the three founders used adapted laboratory evolution and strain engineering—as well as bioprocess engineering around fermentation conditions—to improve the strain’s performance and profile. They focused on both quantitative performance metrics (such as titer, rate, and yield) and qualitative performance metrics (such as triglyceride profile).

The yeast strain isn’t something Ticku discusses publicly. She does note, however, that it is somewhat familiar to the research world. It was characterized in a paper that appeared a decade ago in Nature, and it is of interest to several academic laboratories. But it hadn’t been the basis of any commercial work until it was cultivated by C16 Biosciences.

At C16 Biosciences, the initial focus is on palm oil, but the company has a broader vision—the entire oils and fats spectrum. The company intends to find ways to decarbonize consumer product supply chains. Despite consumers and investors wanting to decarbonize, no one, Ticku observes, is moving quickly enough to address the climate crisis. The first goods to incorporate the company’s oils will be personal care products. (They are expected to be on the shelves within the year). Next, the oils will be in home care and food products.

The company started in Boston because that is where the founders first met. But when the company grew to eight people, a move to NYC was organized. In the summer of 2019, the company’s effects were packed into a U-Haul truck, which Ticku drove down I-95. Ultimately, all eight people relocated.

Why NYC? Ticku says that she “could talk about this forever.” Although she often hears about the difficulties of building a company in NYC, she has found that there are advantages. For example, real estate is relatively available. (C16 had little difficulty establishing a 20,000-square-foot headquarters in midtown Manhattan, whereas arranging laboratory space in Boston involved a two-year wait.) Other advantages, she continues, include an abundance of talent and city and state incentives to support the life sciences. Finally, she enjoys the views. She can see the Empire State Building, Hudson Yards, and beautiful sunsets over the Hudson River from her office.

A bridge between breast milk and formula

Laura Katz started thinking about the infant formula market long before it suffered the supply problems that recently became headline news. A food scientist by training, Katz had an “aha” moment six years ago while riding the N train to Brooklyn. She was listening to a podcast about a black market for breast milk. In this market, parents of children who were not breastfeeding—for whatever reason—were able to buy breast milk from strangers. She learned that many parents believed that this unregulated market was the only way the nutrition they deemed necessary could reach their children.

At the same time, Katz saw the innovation going into alternative dairy and alternative meats in her industry. So, she spent the next few years talking with the founders and CEOs of biotech firms, in addition to parents, to learn how to start a company that could recreate breast milk. In 2019, Katz founded Helaina—named after her great-grandmother.

Laura Katz, Anthony Clark, Pamela B. Besada
Helaina knows that it needs considerable resources to shake up the $50 billion infant formula business. Accordingly, the company is duly encouraged that it raised $20 million in a recent Series A financing round. The company is using the funds to advance its manufacturing and commercialization plans, its market strategy, and its talent acquisition efforts. (Standing in the center of this image is Laura Katz, the company’s founder and CEO.)

Helaina is not another infant formula company. It was started to bridge the gap between breast milk and infant formula. Indeed, Katz asserts that Helaina is able to bring a new kind of product to market because the company uses fermentation to recreate breast milk glycoproteins.

These breast milk glycoproteins have never been made, commercialized, and added to foods before. One of the reasons is that different organisms glycosylate proteins differently. So, if Helaina were to use yeast to produce new food ingredients, the proteins would get glycosylated in a pattern that is native to yeast. To avoid this problem, Helaina has engineered yeast to mimic the human glycome.

Helaina is engineering and developing yeast that can serve as a platform to make human milk glycoproteins. Every glycoprotein will count as a food ingredient and require its own regulatory process. At present, Helaina has one glycoprotein. Besides scaling its production, the Helaina team, which includes 30–40 people, is working to introduce additional proteins. The team has also developed an infant formula base to which the company’s first protein (and subsequent proteins) may be added.

When will Helaina’s product be on the shelves? Katz says that the answer to that question isn’t clear. So much has changed over the past few months, given the recent shortage. Helaina’s next step is to make its product so that it can be tested in clinical studies. The company is, she admits, in a tough spot due to a mandate that all formula manufacturing facilities operational in the United States need to be making product that can be sold. But the company hopes that it will start trials next year.

Will parents adopt a new, synbio-generated infant formula? This is the biggest unknown, Katz notes. But when she talks to parents, they are excited about the opportunity to feed their baby something closer to breast milk.

Helaina was born in the NYC incubator space known as Biolabs. Recently, the company outgrew that space and moved into the Cure building—a new life sciences building that Deerfield Investments opened on Park Avenue. Life sciences communities such as Biolabs and Cure are becoming more common in the city, particularly since NYC and New York State have invested $1.5 billion into supporting biotech in the area as part of the LifeSci NYC initiative.

Why is Katz building her business in NYC? She points first to the unique energy of NYC and the talent that she finds to build her team. She adds that Helaina, which intends to be a consumer-facing company, will benefit from being where the best brands are built. “We could not be anywhere else but here,” she declares. “Once you’re here, it’s hard to leave.”

For some time, thoughts of synbio-generated infant formula have filled Katz’s days. And by now, they may be filling her nights, too. (At the time this article was written, she was expecting her first child in July.) She always thought that Helaina’s product would be ready by the time she had her own children. And while that won’t be the case, she is optimistic that it may be ready for her second.

A new purpose for an old microbial process

The first observations of spore formation in bacteria can be found in the 19th century laboratory notebooks belonging to Ferdinand Cohn and Robert Koch, the “Fathers of Bacteriology.” The process is a well-understood foundation of bacterial physiology. Now, a Brooklyn-based synbio startup is hoping to harness the process, combine it with new technology, and solve the problem of tracking products through supply chains.

Ellen Jorgensen, PhD, CSO of Aanika Biosciences, has been involved in NYC’s biotech scene for decades. She was the founder of Genspace and Biotech without Borders, two citizen science efforts designed to close the gap between science and the public by providing hands-on STEM education. After a decade in that field, she was looking to segue back into for-profit industry.

Vishaal Bhuyan and Ellen Jorgensen, PhD
Microbial-tag specialist Aanika Biosciences was co-founded in 2018 by Vishaal Bhuyan (left) and Ellen Jorgensen, PhD (right). Previously, Bhuyan had experienced the frustration of ordering fresh, ethically sourced seeds and receiving stale, contaminated products instead. He teamed up with Jorgensen, a biotech veteran who was transitioning from citizen science to profit-driven enterprise, to improve food tracking technology. Today, he is Aanika’s CEO, and Jorgensen is the CSO.

Around the same time, Vishaal Bhuyan, a former hedge fund manager in Connecticut, was taking a class at Genspace. He was thinking about solving a supply chain problem. How could goods—particularly those sourced overseas—be tracked closely enough to establish beyond any doubt their places of origin?

Bhuyan wanted to develop a tracking technology for food products. He had in mind edible tags made from a harmless microbe (Bacillus subtilis). The tags would carry a nonfunctional, noncoding snippet of DNA that would act like a barcode or watermark.

What attracted Jorgensen to Bhuyan’s endeavor was “the sheer simplicity of the idea.” The microbe was already in wide use industrially, in probiotic formulations, and known to be harmless. And writing DNA is now incredibly easy.

A Bacillus cell forms a spore when it is placed under conditions that are highly stressful—and the cell senses that it will not survive. The bacterium enters a dormant stage where, instead of replicating, it initiates a mechanism to protect its DNA with a very tough outer coat. It forms a spore. The team at Aanika creates different strains that are genetically identical, except for a very small piece of DNA—less than 200 base pairs—that is embedded in a nonfunctional genomic region through homologous recombination. The spores are mixed into food at the source, and then the shipment-specific barcode can be read out at the other end by qPCR or targeted next-generation sequencing.

Up until now, tracking has faced challenges. Attaching identifying marks to packaging can be problematic. Packaging can be destroyed, or its information can be lost in an aggregation center. There are roughly 70,000 produce farms in the United States. To track produce—leafy greens for example—each farm would need a different barcode. Aanika’s system could clear these hurdles.

Aanika dismisses skepticism about building a biotech company in NYC and denies that real estate is a barrier. The company will soon be opening a 27,000-square-foot facility, with 10,000 feet of laboratory space, that will be the company’s home in addition to a center for food safety and biotechnology. The space will house a pilot fermentation facility that Jorgensen hopes will be a resource or incubator space for other companies that are starting up in the city. Right now, notes Jorgensen, there are no small-scale industrial fermentation facilities in NYC where a company can make just a small batch of a fermented product.

“California and Boston, look out,” Jorgensen exults, “New York City is coming for you.” And it’s coming for you in a very interesting way, she adds. Many of companies that are doing biologically related work in NYC are focusing on industries other than biomedicine. These not your mother’s biotech companies. They have a different look and feel, and they play by different rules—which is fitting, since they are making their way in commercial realms that have yet to integrate biotech and synbio solutions, but soon will.

The post Bringing Big SynBio to the Big City appeared first on GEN - Genetic Engineering and Biotechnology News.

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