Startup bets their superfast microbe can rewrite biotech 

Startup bets their superfast microbe can rewrite biotech 

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When scientists talk about velocity, they don’t usually mean bacteria. But for a small Cornell spinout called Forage Evolution, speed is everything.

The company, founded by three Cornell alumni – Bryce Brownfield, Ph.D. ’23; David Specht, Ph.D. ’21; and Cameron Kitzinger ‘22 – is betting their modified version of one of the fastest-growing microbes on Earth can upend how biologists interact with living systems. Its recent acceptance into Cornell’s Center for Life Science Ventures, the university’s incubator for promising biotech startups, marks its official leap from the lab bench into the commercial world.

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“We’re starting to digitize the bio side of biotech by giving the fastest-growing organism on the planet a molecular Ethernet port for DNA.” Brownfield said.

Forage Evolution’s core innovation centers on Vibrio natriegens, a saltwater bacterium that divides roughly every 10 minutes under the right conditions – about twice as fast as E. coli, the microbial workhorse of modern biology. What makes their V. natriegens remarkable, according to Brownfield, isn’t just speed. It’s the way it takes up DNA from its environment, transforming itself without the expensive equipment or hands-on processing in a biotech lab that’s typically needed.

In a recent paper in the journal PNAS Nexus, Specht demonstrated that by engineering V. natriegens to express a gene known as tfoX – a master regulator borrowed from Vibrio cholerae – they could create a strain capable of performing “natural transformation” in a single, simple step.

In lay terms, the bacterium becomes biologically competent: able to absorb DNA directly from its surroundings and incorporate it into its own genetic code, all while growing in a minimal salt-and-acetate medium.

“This makes it incredibly easy to engineer DNA in a microbe,” Specht said. “This allows people who are not traditional biologists to do real, serious DNA manipulating. And if it becomes easier to do these processes, it’s easier to automate and scale these.”

That process historically takes hours of precise temperature shifts, specialized equipment and significant human oversight spread over several days. The Forage Evolution team’s approach, by contrast, can occur entirely at room temperature with no capital equipment. It’s plug-and-play synthetic biology, according to Brownfield, the method requiring 80% less hands-on time and potentially producing results within a single workday.

The implications are broad. Because the cells can maintain their ability to transform for prolonged periods at room temperature, the process could open the door to low-cost, large-scale and even automated systems for “directed evolution” – the iterative tweaking of genetic sequences to develop new enzymes, materials or chemicals. That kind of work has long been the purview of institutions with expensive infrastructure. Forage Evolution’s system, by contrast, could make high-throughput genetic engineering accessible to smaller labs, educational institutions and developing-world research centers.

“Democratizing biotechnology” has become something of a cliché, but Forage Evolution’s approach gives the phrase technical substance. The team’s method eliminates the need for centrifuges, heat baths and costly electroporators. Instead, the microbe performs its own transformation under physiological conditions, using acetate – a simple, low-energy carbon source that can be derived from electrochemical conversion of carbon dioxide. That makes the system not just faster and cheaper, but potentially more sustainable.

Forage Evolution taps into this magical marine bacterium and develops a simple and efficient way to insert DNA, making it a powerful alternative to E. coli,” said Ying Yang, the CLSV’s director.  “This is a potentially game-changing approach with many impactful applications such as automated synthetic biology platforms, low-cost biotech education kits and sustainable biomanufacturing.”

Acceptance into the incubator gives the young company access to Cornell’s laboratory infrastructure, investor networks and mentorship from biotech veterans. The center, which has helped launch several successful life-science firms, focuses on shepherding university research with commercial promise through the critical early stages of development.

“The incubator gives us lab space, and this would be impossible without that,” Brownfield said. “And they’ve connected us with a lot of impactful mentors, with people on the business development and the legal side. The access to experienced leadership is great. One of the senior executives-in-residence, Bill Rhodes, has a background with products like ours.”

Forage Evolution has a plasmid cloning kit coming out in the next few weeks, Brownfield said. For now, he said, the startup’s focus is on building a suite of tools for other scientists and companies that want to use V. natriegens as a biological “chassis.” The bacterium’s unusual metabolic flexibility allows it to grow on diverse substrates, even nonsterile seawater, making it attractive for biomanufacturing platforms that aim to minimize cost and resource inputs.

In the long run, Forage Evolution envisions using the microbe for producing sustainable bioplastics, biofuels and specialty chemicals.

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Ithaca startup aims to free diabetes patients from daily burden

The Center for Life Science Ventures (CLSV) has admitted a promising biotech startup company with deep roots at Cornell.

Persista Bio is pushing toward a goal that has tantalized scientists for decades: treating Type 1 diabetes – which affects 9 million people worldwide – without daily injections, pumps or immune-suppressing medicines.

If Persista’s technology works in humans, the implications would be profound: an implant that restores insulin production without triggering immune rejection or requiring immunosuppressant drugs. That could dramatically reduce the risk of side effects, improve normal quality of life and lower costs over time, the researchers said.

Persista Bio was co-founded by Linda Tempelman, Ph.D. ’93 and Minglin Ma, professor of biological and environmental engineering in the College of Agriculture and Life Sciences, whose lab developed the foundational encapsulation technology. Dr. Tempelman and her team at Giner Life Sciences developed the enabling oxygenation technology. The two teams got together in 2021 to combine the technologies and have published the resulting work. 

Founded in 2023, Persista Bio is still in the preclinical stage, but it has already made strides that suggest it could be one of the most important players in encapsulated cell therapy, according to Ying Yang, the interim CLSV’s director. Its lead technology, the O2Line™ platform, combines two powerful ideas: protected encapsulation of insulin-producing cells and continuous oxygenation to keep those cells alive and functional for the long term.

“I am proud to see the progress here from research in the lab to a potentially life-changing therapy,” Yang said. “With other technologies, maybe the cells are functional, but the delivery system isn’t – that’s the bottleneck. Persista’s approach offers a promising way to address the delivery challenges. This technology has the potential to really make a difference.”

Type 1 diabetes patients currently must rely on insulin injections or pump systems and constantly monitor blood sugar. Even with those tools, long-term complications – kidney disease, vision loss, cardiovascular damage – remain a serious risk.

According to Tempelman, the core challenge in cell therapy for diseases like type 1 diabetes is that while scientists can establish insulin-secreting cells in the lab from stem cells, keeping them alive once implanted is difficult. The encapsulation that protects them from immune rejection also deprives them of oxygenation; the wrong capsule material tends to cause scar tissue. Both responses degrade the cells’ function.

Persista’s O2Line system addresses both. It uses a nanofibrous capsule designed to protect the implanted cells from immune rejection while allowing nutrients and insulin to cross the capsule barrier freely. The system also includes an implantable electrochemical oxygen generator licensed from Giner, Inc., which supplies oxygen directly to densely packed cells. In a study published in August in Nature Communications, the Persista team reported that their system reversed diabetes in rats without requiring immunosuppression.

“What we’re doing is encapsulating the cells with a membrane that has special properties so the body doesn’t reject the cells,” Tempelman said. “This means you won’t need immune suppression—that is a huge advantage over the approaches taken by other companies. That opens up this treatment to the vast majority of people with T1D. In our system, these oxygenated stem cells sense glucose and put out the right amount of insulin acting like a normal pancreas.”

Persista Bio is licensing its technology from Cornell and Giner Labs. Tempelman previously commercialized a transdermal sensor technology at Giner and holds eight U.S. patents. Ma has spent over a decade studying cell encapsulation. Another co-founder, James Flanders, emeritus associate professor at the College of Veterinary Medicine, brings experience in large-animal studies relevant to how devices behave in living bodies.

Persista Bio recently secured two grants from the National Institutes of Health (NIH). One of them, a $2.1 million Direct-to-Phase II Small Business Innovation Research (SBIR) grant from the National Institute of Diabetes and Digestive and Kidney Diseases, will support scale-up to large animal models, validation of the device in minipigs and work on manufacturing under good manufacturing practices (GMP) standards.

“The Direct-to-Phase II grant is to prove proof of concept in large animals,” Tempelman said. “As part of the incubator, the team will be onsite in Ithaca, and we will perform preclinical testing at the College of Veterinary Medicine. That’s a prime opportunity. With the other grant, Persista will move toward commercial manufacturing of the capsule with a specialized grant that includes Ying Yang as a mentor to new entrepreneurs and principal investigator Beum Jun Kim Ph.D. ’04, vice president of engineering at Persista.” 

According to Tempelman, the O2Line platform could apply to other diseases where cell therapies are constrained by oxygen or fibrosis, such as metabolic disorders, enzyme deficiencies, inflammatory diseases or chronic pain.

Over the next two years, Persista Bio aims to complete large-animal model studies, build its human system prototype and move toward clinical trials. Successful trials would not only validate the technology but could also help the company partner with larger biopharma or device companies, potentially licensing the system or collaborating to bring it to market in diabetes treatment and beyond.

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