Stefan Roever, CEO of the bleeding-edge gene sequencing company Genia Technologies, first made his name as a software entrepreneur. When he talks about the future growth of Mountain View, CA-based Genia, he envisions a dynasty similar to the one founded by the tech giant Apple of Cupertino, CA.
Roever’s ideal dynasty, like Apple’s, would be based on a novel device, a high-grade operating system, and a vast constellation of apps.
A business empire could be founded by the company that develops a cheap, highly accurate gene sequencer about the size of a sci-fi medic’s tricorder in an old Star Trek episode, Roever says. For about $100 a test, it would decode a human genome—or quickly sequence the genes of a germ plaguing a patient who gives a blood sample to a clinic nurse. The sequence would be uploaded into a universe of cloud-based diagnostic applications that could identify the microbe by the time the patient gets in to see the doctor.
Genia is trying to build that first-in-class, best-in-class device. It’s one of the companies in a race to transform gene sequencing from a costly activity in research labs to a routine part of clinical medicine. The company, founded in 2009, will share in a recently awarded $5.25 million NIH grant with scientists from Harvard Medical School and Columbia University who have already developed much of the technology that makes Genia’s gene sequencing device a contender in that race.
“I think the winner here is going to be the company that can make a cheap enough, accurate enough ecosystem where anyone can have access to it,” Roever says. The NIH grant will help Genia fine-tune its prototype sequencing system, in which DNA strands are rapidly analyzed by integrated circuits on semiconductor chips.
“It’s a convergence of IT and DNA,” Roever says.
Genia’s instrument is an alternative to current gene sequencing methods that involve costly, time-consuming steps, such as producing many copies of the genetic material under study to ensure accuracy. In another series of steps used by older commercial sequencers, the four different “letters” of the DNA code are labeled with four different fluorescent tags, one type of tag at a time. These tags can be distinguished from each other by the light sensors used in most gene sequencing machines on the market.
The device developed by Genia, now about the size of a desktop printer, can sequence a single DNA strand, eliminating the need to make multiple copies. Genia routes each single piece of DNA to an individual well on a microchip containing many wells. Electrodes in each well identify the sequence of “letters,” or nucleotides, in the strand by detecting changes in an electrical current, rather than using light sensors.
“Our view is that the market is, in the longer term, moving toward single molecule, electrical detection,” Roever says.
Similar shifts in sequencing technology are being pursued by other companies such as Oxford Nanopore of Oxford, UK and Providence, RI-based Nabsys. Like Genia, these companies are moving gene sequencing into a high-tech world that blends computer technology with synthetic biology in the same nanoscale device.
The first semiconductor-based gene sequencer was introduced into the market in 2010 by Carlsbad, CA-based Life Technologies (NASDAQ: [[ticker:LIFE]]), which acquired the technology when it bought Ion Torrent Systems of South San Francisco and Guilford, CT. The inexpensive, benchtop Ion Proton systems now compete with rapid sequencing machines made by industry leaders such as San Diego-based Illumina (NASDAQ: ILMN). But the Ion system still requires multiple copies of the DNA strands being analyzed, and multiple, separate steps to identify each of the four nucleotides that make up the DNA alphabet.
To read single strands of DNA, Genia and other startups use a key element called a nanopore—a tiny channel through which an electrical current can flow and be measured by an electrode in a microchip. When a biomolecule enters the nanopore, it alters the current flow in a pattern characteristic of that molecule.
The potential of nanopore-based sequencing got a big vote of confidence recently when NIH’s National Human Genome Research Institute awarded a total of $17 million in funding under its so-called “$1,000 Genome” grant program to eight separate research groups, including Genia’s collaboration. Of those grant recipients, five are tinkering with nanopores. The largest grant of $5.25 million went to the inventors of the core technology used in Genia’s instruments—Jingyue Ju of the Columbia University school of engineering, and synthetic biology leader George Church of Harvard.
The NIH is trying to help companies bring the cost of sequencing an individual human genome down to $1,000. The current commercial price is still at least $4,000 to $5,000. Price is still an obstacle for physicians who would like to have patients’ genetic data to help them reach a diagnosis or choose the best medicines.
The current cost of thousands of dollars is a triumph, however, when you consider that the Human Genome Project achieved the first sequencing of a human genome only 10 years ago, through the combined efforts of an international consortium of research labs at a cost of $1 billion. By 2009, the price was $100,000. Next-generation sequencing companies such as Illumina and Life Technologies have brought that cost into the four-digit range. Now several of the recipients of the NIH’s $17 million grant round, including Genia, are aiming for the $100 genome.