Cleaner Water Through Biotech? 349Q Kills Water-Borne Microbes with RNAi

4/27/09Follow @wroush

“Biotechnology” and “water purification” aren’t usually themes that you hear mentioned in the same sentence. There are plenty of biotech startups aiming to use cutting-edge molecular approaches like RNA interference (RNAi) to develop profitable new drugs—but fewer people, if any, talk about how these technologies might help people in developing countries where safe drinking water is in short supply. Indeed, at first blush, the idea that molecules as fragile as snippets of RNA could be used on an industrial scale to kill pathogens in water seems farfetched.

But that’s exactly what a Somerville, MA-based startup called 349Q hopes to do. In stealth mode until last week, the company has now begun talking to reporters about its plans, which call for identifying genes common to the main species of dangerous microbes found in water, then engineering viruses that could manufacture RNA strands capable of shutting down the microbes’ basic metabolic processes. The company’s technology, for which it has obtained provisional patents, grows out of work in the laboratory of Claudia Gunsch, a microbial engineering expert in the Civil and Environmental Engineering department at Duke University in Durham, NC. Mark Modzelewski, a cleantech and venture capital veteran based in Somerville (and an Xconomy guest essayist), is handling the company’s fundraising and business development.

With supplies of fresh, clean water chronically limited around the world, water purification is obviously an area crying out for new technological solutions. In a Technology Review interview published last week, prominent Silicon Valley venture capitalist Steve Jurvetson called water purification “a trillion-dollar opportunity” and said the water industry exhibits “probably the biggest mismatch between a screaming, enormous market and a lack of technology innovation I’ve ever seen.”

There’s no shortage of technologies for purifying contaminated water—they include distillation, carbon filtration, membrane filtration, ultraviolet irradiation, reverse osmosis, and ion exchange. But all have their shortcomings, ranging from high cost and high energy consumption to low flow rates.

Modzelewski says he has spent years on the lookout for a new water purification technology that merits a venture capital investment. Over breakfast last week, he laid out his criteria for such a technology: “It needed to cost the same as anything we have now; it needed to be very easy to attach to current water-treatment systems, without requiring any expensive retrofitting; and it had to be completely different.”

The idea that RNA interference might provide a solution is new, radical, and largely untested. A lot of the drama in pharmaceutical research on RNA interference is around how to shepherd RNA molecules past all the blood-borne enzymes that would normally chew them up and deliver them safely into cells, where they can then disrupt the activity of targeted genes. Delivering the molecules inside the body has been such a preoccupation for researchers, according to Duke’s Gunsch, that there wasn’t any data on whether they could be disseminated to microbes through water.

That’s the experiment Gunsch and Sara Morey, a PhD candidate in her lab, first tried last year. They filled a sample of water with a strain of fungus that had been engineered to produce a particular yellow protein. They then added RNA snippets that had been custom-sequenced to silence the gene responsible for the protein’s production. The water’s color changed instantly—indicating that the RNA had readily gotten inside the fungus cells and was turning off the targeted gene. (In purification applications, the RNA snippets would be designed to turn off genes critical to microbes’ survival.)

“A lot of the RNAi guys we’ve talked to are very stunned by that initially, because they didn’t think it would work for that long in water,” says Modzelewski. “And it doesn’t—but it lasts a few seconds longer than is needed for the killing effect.”

Modzelewski learned of the technology after Morey presented the fungus experiment at the annual meeting of the American Society of Microbiology in Boston last June. He says the idea seemed to meet all his criteria—so he contacted Gunsch about starting a company.

To say that 349Q has a lot of work to do to see whether RNA interference can be harnessed for large-scale water purification would be an understatement. For one thing, Gunsch’s team needs to identify a manageable number of gene targets in fungus, bacteria, and other waterborne pathogens. “The idea is to hit multiple pathogens at the same time,” says Gunsch. “There are genes, for instance, involved in DNA replication and very basic metabolic functions that are present in many organisms and those are the ones we will be targeting.”

Then the company needs to figure out an economical way of making mass quantities of the RNA fragments needed to silence those genes. Gunsch is deliberately vague about 349Q’s plans in this area, but she says the company hopes to develop genetically engineered viruses that could be embedded in a fibrous material, where they’d churn out customized RNA fragments as contaminated water streams past.

Then the company has to determine how fast water can be pushed through such a device while still killing all the microbes. “It’s really going to be all about the residence time—how long you need to be in contact with the target,” Gunsch says. “There is going to be a lot of engineering going into that.” But that’s okay, since Gunsch was actually trained as an environmental engineer rather than a molecular biologist.

349Q is in negotiations with Duke to obtain an exclusive license to commercialize the technology, and has obtained just under $200,000 in seed funding, according to Modzelewski. That money, plus some hoped-for Department of Energy funding, should be enough to help 349Q complete proof-of-concept work and get the company to the point where it’s ready to seek serious venture funding, Gunsch says.

While she hopes that the technology will ultimately help communities in developing countries where obtaining safe drinking water is a problem, the first applications would probably be more limited. For example, the technology might well suited for filtration systems for water towers or air-conditioning systems, where virulent bacteria like Legionella are a danger.

Water purification companies have little choice but to follow the money if they want to reach scale, Modzelewski says. “Unfortunately, society has made water largely free,” he says. “While I’d be one of the first people to fight for people’s right to water, the ultimate side effect of making it free is that nobody wants to pay for it or do anything to make it better.” Companies that make water-handling equipment are “more willing to pay” for new technologies, he says.

Though it’s done virtually no marketing, 349Q is already winning some attention in the water world. The Artemis Project, a boutique water technology consulting firm in San Francisco, named the startup one of the top 50 water companies worldwide in a competition that finished last week.

So, what’s up with the funny name? According to Modzelewski, 349Q is a reference to the estimated volume of water on Earth in gallons—about 349,000,000,000,000,000,000 or 349 quintillion.

But the name may actually be a bit of a misnomer, since 97 percent of the planet’s water is salt water, and 349Q’s technology does not tackle the desalination problem. That’s the province of Cambridge, MA-based Oasys—which, in February, closed a $10 million funding round with participation by Steve Jurvetson’s firm, Draper Fisher Jurvetson. Whether Jurvetson and his ilk will also see RNAi as a new path toward exploiting the “trillion-dollar opportunity” is an open question.

Wade Roush is a contributing editor at Xconomy. Follow @wroush

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