If the genetic revolution has yet to deliver fully on its promise, Cullen Buie, associate professor of mechanical engineering, may know one reason why: “In the last 30 to 40 years, our ability to innovate with the genetic code has gotten faster and cheaper, whether reading or writing DNA,” he says. “But it’s kind of a dirty secret that for decades there’s been virtually no innovation in the methods for putting DNA into cells to reprogram them.”
This state of affairs may be about to change. Buie and research scientist Paulo Garcia have developed a platform that simplifies and accelerates the process of introducing DNA or other molecules into cells. This new technology may well break the bottleneck in genetic engineering, vastly improving the process of drug discovery and opening up new frontiers in synthetic biology. “Our vision is to make delivery of foreign media into cells faster and easier for all applications,” says Buie.
To realize this vision, Buie and Garcia recently formed a company called Kytopen, one of seven startups to receive seed money from MIT’s newly minted “tough tech” accelerator, The Engine. Dedicated to supporting innovative ventures with potential for societal impact, The Engine seeks out startups whose breakthrough ideas require time to commercialize.
The heart of the Kytopen platform is an ingenious twist on electroporation—the process of shocking individual cells with tiny amounts of electrical current to open their pores, which permits the introduction of customized DNA or other media. Typically, this process is accomplished by hand, in small batches, with technicians adjusting the current to find just the right amount of juice for zapping the cell open without killing it.
Building on expertise devising microfluidics tools for use in small-scale biological systems, Buie’s lab invented a tiny pipette equipped with electrodes through which cells flow. As cells move through the pipette’s tiny channel, they are exposed to an electric field with just the right amount of current to open their pores. “So now we can continuously flow cells and deliver DNA into them for reprogramming at a rate that is 10,000 times faster than current state-of-the-art industrial technology,” says Buie.
The idea is to scale up the Kytopen platform for high-throughput, high-volume assembly line work, with legions of fluid-handling robots modifying vast batches of cells. For researchers seeking to identify useful new properties in microorganisms or to modify microbes for the purposes of creating novel molecules, this kind of mechanization would prove invaluable.
“The scientific community has characterized maybe 1% of bacteria on the planet, and we’ve been able to exploit only 1% of that for genetic engineering, so there’s a tremendous amount of biological diversity we have yet to harness,” says Buie. “Testing DNA sequences and designing nucleic acid to generate a product of interest requires you to make many iterations, and Kytopen could really move things along,” he says. In addition to ferreting out a treasure trove of DNA in microbes that could help develop new drugs or energy technologies, says Buie, the Kytopen platform could also quicken the pace of synthetic biology, facilitating the repair of harmful genetic defects or the creation of bioengineered parts for medicine.
For Buie, the notion of lowering barriers for the discovery and creation of important new applications is energizing. “Before coming to MIT, I thought carefully about areas likely to have a huge impact on society in my lifetime,” he says. “Clearly engineering of biology would play a major role in our generation’s technological problems and solutions, and I wanted to get into it.”
The next phase for Kytopen, says Buie, involves choosing “a killer application that is so well suited for our technology that it is clearly the best solution,” he says. As a first-time entrepreneur, he’s nervous, but excited. “There’s a lot of moving parts, and while we have a vision and a goal, we don’t know how it will turn out,” he says. “But I’ve gotten used to working with uncertainty.”