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Tuesday, 10/14/2014 8:01:56 AM

Tuesday, October 14, 2014 8:01:56 AM

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Biotech Startups Tap Spider Genes in Quest to Spin Silk Gold
Angela Shah-10/14/14

Click For xconomy.com Link


Silken threads-Kraig Labs' "Monster Silk" ready for weaving. Photo: Kraig Biocraft Laboratories


A modern-day Silk Road is emerging, and traffic on it is building up.

These explorers aren’t traversing routes across continents, but instead are seeking scientific and agricultural alchemy to produce a sort of holy grail in apparel: commercial amounts of spider silk.

Spider silk is a multi-purpose fiber able to be transformed into surgical bandages, sports gear, musical strings, or body armor, says David Brigham, founder and CEO of EntoGenetics in Charlotte, NC. The military uses, in particular, motivate Brigham, a biochemist and geneticist by training. “Soldiers need better, lighter protection,” he says.

Spider silk has long been the ultimate textile target. Its beauty was coveted by royalty; Louis XIV of France supposedly had gloves, stockings, and even a full suit made from the weaves of the golden orb spider of Madagascar.

These days it’s the silk’s strength—touted as five times as strong as steel, and as tough as Kevlar but more elastic—that’s attracting attention. Stopping a runaway train from flying off the tracks using spider webs may not only be the realm of Hollywood.

But replicating that material on a scale useful for a modern-day superhero, or mere mortal, has been elusive. Spiders don’t really take to being domesticated for farm work (they get restless minutes into the “milking” process and tend toward cannibalism), so it’s difficult to harvest enough thread for a commercial apparel operation.

If it could be done, though, the stakes are huge. In the U.S. alone, the market for advanced protective gear and armor was worth $4 billion in 2010 and is expected to reach $5.2 billion next year, according to consulting firm BCC Research.

Protective gear for soldiers, as well as police and firemen, is among the top potential uses for spider silk. The fiber could also be used to make high-end performance sports apparel and, further down the line, to contribute to a host of medical applications from sutures to wound dressings. Spider silk is not rejected by the human body, so there’s also potential for artificial tendons, implant coatings, or biomedical scaffolding for organs or skin.

The question is how best to produce the material. Brigham at EntoGenetics says his team has developed a way to take the genes that allow spiders to make such strong silk and implant them into the chromosomes of silkworms, which serve as more willing factories, to produce reconstructed “spider” silk. (Spider silk is stronger, and so preferable, to that made directly by silkworms, he says.) Brigham says EntoGenetics is trying to create silk that is 100 percent from spider genes as opposed to a hybrid of spider and silkworm genes.

The North Carolina startup has plenty of competition. Kraig Biocraft Laboratories in Lansing, MI, is also trying to produce spider silk through transgenic silkworms to make a fiber that is a composite material. “It’s spider DNA spliced into the silkworm so the silkworm produces spider protein but also produces its own proteins,” says Kim Thompson, Kraig Labs’ founder and CEO.

The result, he says, is that the spider silk proteins reinforce the silkworm fiber like rebar in concrete. “With a small percentage of spider silk proteins, the result is a dramatic increase in strength, flexibility, and energy absorption levels,” he explains.

Kraig Labs—which has two employees, Thompson and his office manager—was founded in 2006 and is based on technology developed at the University of Wyoming (more on that below); the company went public on the OTC markets two years later. Kraig Labs currently has partnerships with scientists at the University of Notre Dame for research and development.

The biotech firm is currently working with Warwick Mills, a New Hampshire materials company, to produce what it calls its “Monster Silk” fabric. Warwick Mills produces high-tech textiles for military, law enforcement, fire department, and other specialty uses. “We are ramping up for commercial scale now,” with plans to be on the market next year, Thompson says.

To boost the company’s infrastructure in order to mass produce its silk, Kraig Labs is in negotations with the government of Vietnam to set up a production facility there could help alleviate that bottleneck. “Vietnam has a large idle capacity for silkworm production—and they have substantial expertise,” he says.

Along with Entogenetics and Kraig Labs, there are a handful of other companies in various stages of producing spider silk using myriad techniques. AMSilk, which is based near Munich, Germany, is trying to develop commercially scalable spider silk through a process that makes spider silk proteins with genetically altered E. coli bacteria; the relevant spider genes are inserted into the bacteria, which are grown in fermenters. The proteins are then spun to make silk fibers. AMSilk currently sells its silk proteins for use in shampoos and cosmetics and is developing products for wound care and other surgical needs, according to its website.

Meanwhile, the Korea Advanced Institute of Science & Technology (KAIST) is working with a Japanese startup called Spiber to also develop spider silk through an E. coli fermenting process. Spiber has so far raised $8 million from Japanese investment banks and plans to open a pilot facility next year.

But Randy Lewis has perhaps been after the spider-silk holy grail the longest—and he has what must be the most unusual approach. In 1990, he was part of a team at the University of Wyoming that cloned spider genes related to silk production. His research found its way into a few startups including Nexia Biotechnologies, based in Quebec, Canada. The company attempted to breed “spidergoats”—goats that were altered with spider genes in order to produce the silk proteins in the animals’ milk. In 2006, Nexia was acquired by Canadian oilfield services company Enseco Energy Services in a reverse merger transaction. Lewis says Enseco was uninterested in the spider silk project.

Lewis’s research at Wyoming lives on at Kraig Labs—and he used to sit on the Michigan company’s board. Today, however, Lewis is a professor at Utah State University in Logan, UT, where he has spun out a competing company called Araknitek. This startup is pursuing a number of different methods to produce spider silk, including the “spidergoats,” several of which Lewis got custody of from Enseco.

Named “Snow,” “Jessie,” and “Ruby,” they seem like normal goats, and they are—with one crucial difference. Lewis’s team placed the gene that encodes spider silk into the DNA that controls milk production in the animals’ udders. So when the goats lactate, their milk contains spider-silk protein that can be extracted in a lab. The fat is separated from the whey, and the protein solid is washed and freeze dried. The solid is then dissolved and silk fibers are spun from it.

His Utah startup, Araknitek, is also pursuing other methods to boost production of the spider proteins, including transgenic alfalfa, bacteria, and silkworms. His lab has received nearly $4 million in federal grants, including $1.9 million in August from the U.S. Department of Energy to see if spider silk fibers could replace carbon fibers in making vehicle components.

Lewis says the different methods can produce silk with different properties, which would have different uses, particularly in biomedicine. Some combinations of spider genes can provide less strength but high flexibility—like one would need in a tendon, say—or the opposite, like what is needed to support ligaments, he says.

The materials entrepreneurs say commercial spider silk, and its superhero-like properties, is definitely coming to market; it’s just a matter of time before someone creates enough of it to make a viable product. Not surprisingly, each says his respective company has the formula to do so.

It will not be easy going for any of them. Industrial giants like DuPont and BASF reportedly have abandoned efforts to create spider silk.

Brigham, for his part, rekindled his interest in the material in 2005, when he says he realized that no one had developed a fiber that was 100 percent spider silk, which he says is the strongest and most flexible material. So, he formed EntoGenetics, receiving a $22,500 business development loan from the North Carolina Biotechnology Center, and has secured a small amount of angel fundraising. This year, EntoGenetics won a $309,000 contract with the U.S. Army for a pilot-scale production of its spider silk to make ballistic shoot packs for soldiers.

Though the company now has its own R&D lab, as well as an orchard of mulberry trees—silkworms’ favorite food—EntoGenetics had humbler beginnings. The company got started in Brigham’s home, where he built out a bar in the basement to house clusters of spiders and worms. The arrangement made for some awkward times in the family’s kitchen, where Brigham cooked up the worms’ special food.

“When it was cooking in the microwave, it made a vegetal aroma that all the kids complained about,” he says. “I always told them it was the smell of money.”

Angela Shah is the editor of Xconomy Texas. She can be reached at ashah@xconomy.com or (214) 793-5763.




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