By Ben Butkus
DNA Electronics will begin pre-clinical pilot trials later this year to prepare its rapid, handheld, semiconductor-based DNA testing platform for clinical diagnostic use, the company said this week.
To that end, the London-based company will collaborate with the lab of Eric Topol at Scripps Research Institute in the area of pharmacogenetic analysis for Plavix response; and with an unspecified lab at St. Mary's University College in London in the area of infectious disease testing, PCR Insider has learned.
PCR Insider spoke with DNA Electronics CEO Chris Toumazou and CTO Leila Shepherd this week following the company's announcement that it had inked an agreement granting skincare company GeneOnyx access to its point-of-care genetic testing device, called Genalysis, to provide rapid, over-the-counter genetic testing to consumers for the purposes of recommending genetically tailored cosmetic products.
The deal with GeneOnyx is the "first significant license" for DNA Electronics' testing platform, but is just the tip of the iceberg, Toumazou said, as the company is now in the throes of honing the platform for in vitro diagnostics use.
"We've been in stealth mode, and we're excited that [Genalysis] is working now," Toumazou said. "The key objective still is to tackle the healthcare and clinical market. But in the past year there has been all this hype about handheld genetic devices, but … we don't know anything to date that actually works. We wanted to make sure the world sees that we have something that works, and works well, so we're applying it to a setting that can demonstrate that. That's why we decided to partner with GeneOnyx."
DNA Electronics' current molecular diagnostics work actually brings the company full circle to its earliest days, when it spun out of Imperial College London to commercialize the discovery that when nucleotide pairs come together during DNA synthesis, they release hydrogen ions, which can be detected as an electrical signal on a complementary metal-oxide-semiconductor, or CMOS chip.
"We patented that idea, and we spun out DNA Electronics in 2002 with aspirations from the very beginning to create a handheld diagnostic technology," Toumazou said. But, he added, the company first applied the technology "to what [we thought] was the really growing field, which was DNA sequencing."
As a result, DNA Electronics negotiated first a non-exclusive license with Ion Torrent, which adopted the technology as part of its next-generation sequencing platform — now called the PGM and sold by Life Technologies, which acquired Ion Torrent in late 2010. After that deal, DNA Electronics then forged a partnership with Roche 454 to integrate the technology into a competing sequencing platform.
"While all that was taking place, which was really a good way of bringing in revenues, we had … a team incubating our holy grail, which was this microchip-based diagnostic device," Toumazou said.
However, the company quickly realized that if it wanted to adapt its technology to a truly handheld, point-of-care testing device, "then clearly just blind sequencing on a chip was not good enough," Toumazou added. "We needed [integrated] sample prep and amplification."
For the amplification component, company scientists discovered that the ions produced during DNA synthesis were also produced during amplification. "So simultaneously we could use the same ions to effectively amplify and detect," Toumazou said. "That common denominator … enabled us to, for the first time, integrate the entire amplification onto a microchip." That process is described in a US patent awarded to DNA Electronics last February, entitled "qPCR using solid-state sensing." (PCR Insider, 2/17/2011)
Next up was the sample prep, which DNA Electronics' Shepherd described as having "exquisite mechanical complexity" inside, but "very simple user operation" on the outside.
"Although we're proud of … all the things you can do with the semiconductor chip — replace the heat block [typically needed for thermal cycling], replace the optics, replace the [fluorescent] labels with a chip that both amplifies and detects DNA simultaneously — the other key piece is the sample prep," Shepherd said.
"You literally just take a mouth swab, put it into the sample prep kit … which is the size of a small cup, and after you twist the cap of the sample prep kit, a series of mechanical steps takes place that replaces, effectively, several scientists' worth of pipetting and other sample prep," Shepherd explained.
The sample prep kit then mixes the sample with nucleic acid extraction and amplification reagents, and then dispenses a small volume of the mixture onto the semiconductor test cartridge, which the user then removes and plugs into an electronic reader such as a USB stick.
"The cartridge seals and creates discrete amplification reaction chambers, each one having its own sensor and own primers, and that's how you get the multiplex reaction," she said. "Effectively it combines the speed of real-time PCR with the multiplex ability of a microarray, because you can put any number of sensors or reaction chambers on a single chip."
Users can then plug the electronic reader into the port of a laptop or other readout device to view results. DNA Electronics claims that Genalysis will produce a result in about 30 minutes; can be operated by minimally trained technicians; and will be relatively inexpensive to manufacture.
On the topic of cost, Toumazou didn't provide specifics, but noted that semiconductor chip costs are currently falling in the same way that the cost of laptop computers have rapidly decreased over the past few years. "In this business it's very much around node size of semiconductors," he said. "We've got unmodified reagents in everything. So that combination could lead us to a marketplace where we could price … how we want to price. It's not necessarily dictated by the bill of materials. It's dictated by how the market would value that."
The next step for DNA Electronics is to validate the testing sensitivity and specificity of Genalysis. As reported in 2009 by PCR Insider sister publication PGx Reporter, the company has already done this to some extent through a partnership with Imperial College London and Pfizer to test a prototype of the device for point-of-care testing of patients for genetic predisposition to adverse drug reactions.
That project, which was funded by a £1.2 million ($1.7 million at the time) grant from the UK government, explored the use of an early version of Genalysis to test samples that had already been SNP genotyped by Pfizer in a reference lab. The device correctly called 100 percent of the blindly tested samples, data that DNA Electronics presented at the Molecular Diagnostics World Congress in South San Francisco, Calif., in September 2011.
Now, DNA Electronics has established a relationship with Topol's lab at Scripps to conduct a pilot trial of Genalysis to measure CYP2C19 genotypes in order to predict Plavix response in about 100 patients receiving cardiac stents, Topol said.
"Before they go in for their stent we're going to know what their genotyping is for responding to Plavix," Topol told PCR Insider. "That will be the first study, and we hope to start that soon. We've already seen [DNA Electronics'] device … and have a protocol laid out.
"After that we'd like to do a much bigger validation trial of how that rapid genotyping changes medical practice," he added. "There's a lot of actionable information, but you want to be sure to show how that improves the outcome for patients."
Topol said that his group has already conducted similar work with another unspecified rapid genotyping system, but said that it was "very cumbersome" and took about an hour to perform. The prototype Genalysis device, he said, "looks eminently simpler, and much more user friendly and fast — it couldn't be much more straightforward."
Topol added that "one of the reasons that Plavix genotyping has not gone mainstream — and this is a similar issue in many clinical environments — is because by time the genotype comes back three days later, the story is mostly over, a lot of doctors think." The Genalysis platform has the potential to provide valuable insight up front, "before you even put in a stent, of how to treat the person before you start the wrong therapy or dose."
DNA Electronics is also working with St. Mary's University College to test Genalysis for infectious disease diagnostics; and, Shepherd said, eventually plans to offer a pipeline of tests — "everything from drug-metabolizing enzymes for drug side effects … to the types of infectious diseases you would want to test outside of a lab, like respiratory panels and [sexually transmitted infections]."
She added that the company is also "happy to work with partners on custom assay development … like companion diagnostic kits, or specific pathogen targets. We also intend to submit the device and certain test panels for IVD certification. The roadmap for this technology is an IVD-approved, CLIA-waived device."
However, Shepherd added, "we want to do field evaluation and get early user feedback before going through the regulatory process … thus the pilot studies and the early-access program we have in place with some customers."
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