Twist Bio Aims for Better DNA Synthesis With Silicon Engineering

5/27/14Follow @alexlash

[Corrected 5/27/14, 6:32pm. See Below.] Like so many other biological building blocks, genes have become just another lab material to order from a specialty shop. Several sophisticated companies can synthesize practically any sequence and ship them to customers for all kinds of experiments, but San Francisco startup Twist Bioscience thinks it has broken through the noise.

The firm announced Tuesday Series B round of funding of $26 million to push forward its genetic synthesis technology, essentially unveiling it with a message of faster, cheaper, better. On the surface, that’s nothing new. A year ago, the Cambridge, MA startup Gen9, which boasts marquee academic co-founders, landed financial and scientific backing from research tool giant Agilent Technologies of Santa Clara, CA, and others have been jockeying for market and mind share. [A previous version of this story misspelled the name of Gen9. We regret the error.]

Twist CEO Emily LeProust (pictured) says her company has leapfrogged the competition with silicon engineering. When a customer designs the DNA variants it wants to experiment with, Twist’s pitch is to synthesize and turn around those custom variants faster and with fewer errors because it has refashioned a “plate”—one of a research lab’s most basic items—from silicon instead of plastic and shrunk it to the size of a postage stamp. (On a visit last week, I held the plate in my hand and asked if I could snap a picture; LeProust said no.)

Instead of 96 wells—the divots that house tissue samples or other material for high-throughput testing—Twist’s silicon plates house 96 wells that look like dots, and each contains 96 more microscopic wells, for a total of more than 9,000 wells per plate. The company is building a machine, which at six feet per side would be just a bit smaller than a SmartCar, that handles the synthesis work. Initially there will be one plate per machine. Twist looks to be open for business next year.

The technology could apply to any field using synthetic DNA in biological processes to create products, even carpets. (A key component of a type of nylon is adapic acid, which at least one company is trying to produce with genetically engineered enzymes that ferment biomass.)

While industrial chemicals, agricultural bio, and diagnostics are all business areas for Twist and its competitors, biopharmceuticals present a broad range of near-term applications. In vaccine production, for example, a drug maker needs to test vaccines against not just a virus, but many subtle genetic variations of that virus, and LeProust says Twist customers would be able to test against a lot more variations with each vaccine run.

Another potential biopharma application for Twist is in biologics manufacturing. Companies like Genentech use giant vats, or bioreactors, filled with genetically engineered living cells—the bacterium E. coli or Chinese hamster ovary cells are two common cells—to produce protein-based drugs. But biologics makers always want to boost the yield and quality from their bioreactors, and just like the components of an assembly line, the cells themselves are subject to improvement.

“People have to go through the design-build-test cycle, that’s what all our customers do,” says LeProust, a native of France who has taken American citizenship. “They design a number of mutations in DNA for different sequences, they outsource the building of that DNA to companies like us, and once they receive the DNA back in house, they test it to find out of all those mutations, which ones do what they want. Then they go back to design-build-test and go through that cycle multiple times.”

LeProust also says the new system is less error-prone, because temperature control, so important with DNA samples, is easier with silicon plates than plastic. LeProust and one of her co-founders, chief technology officer Bill Peck, are Agilent alumni; when asked if she was surprised that her competitor Gen9 collaborated with Agilent last year, she preferred to comment on the merits of Twist’s new system. The third co-founder of Twist is Bill Banyai, who worked with Peck at Complete Genomics and leads Twist’s silicon engineering efforts.

Twist’s $26 million B round was led by Nick and Joby Pritzker, through their family’s Tao Invest fund, and also included ARCH Venture Partners, Paladin Capital Group, Yuri Milner and other undisclosed investors. Twist also has in hand a $5 million grant from Defense Advanced Research Projects Agency, or DARPA, the federal agency whose early support has brought to fruition some of the world’s breakthrough technologies.

The grant comes from DARPA’s “Living Foundries: 1000 Molecules” program, which according to the DARPA Web site, aims to build an infrastructure “for the facile engineering of biology. This infrastructure will be defined by tools and processes to make possible a scale and sophistication of experimentation that does not exist today.” The “1000 molecules” reference is the program’s goal: “To demonstrate the power of the capabilities being developed, the infrastructure will generate 1000 new molecules of relevance to the DoD, including chemical building blocks for accessing radical new materials that are impossible to create with traditional petroleum-based feedstocks.”

The DARPA grant and Series B bumps Twist’s total funding to about $40 million. The company pulled in a $9 million Series A round in 2013. It aims to hire 80 employees by the end of 2015.

Alex Lash is Xconomy's National Biotech Editor. He is based in San Francisco. Follow @alexlash

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