Back in 2003, Caltech’s Steve Quake had the first claim to a publication showing DNA sequencing at the single-molecule level. Now, the company founded in late 2003 and funded with $27 million to commercialize that technology says it is poised to make the first major impact in bringing sequencing (or, more specifically, resequencing) to the masses.
Helicos BioSciences, founded by Quake, Eric Lander, financier Noubar Afeyan, and biotech entrepreneur Stan Lapidus, is based in Cambridge, Mass., where scientists are working on their third version of a sequencing instrument based on Quake’s original efforts. By the end of this year, says CEO Lapidus, Helicos expects to be shipping its first instrument to Eric Lander’s lab. (Lander has no financial ties to Helicos, Lapidus notes.) If all goes well, the plan is to have beta instruments out by next year and a commercial system available in 2007.
Anyone who’s been following this field can think of several other sequencing startups vying for the vaunted $1,000 genome. But Helicos, which technically speaking has much the same goal, is approaching the problem with a slightly different focus: cancer. “There’s been little penetration of mainstream sequencing instruments in the clinical market,” says Lapidus, whose previous startups focused on cancer detection tools. If the next version of Helicos’ technology meets its goal of sequencing 30 billion bases per day — making viable the concept of sequencing the genome of every individual and every tumor — Lapidus says, “That would break the back of the cancer genome.”
Currently, Lapidus says, the tool is capable of reading 3 billion bases per day using a sequencing-by-synthesis method. That’s accomplished by placing 1.2 billion 25-mer strands of DNA on a substrate, adding a terminal transferase, priming each strand, and interrogating the mix with red and green lasers. “We wanted to do true single-molecule imaging,” Lapidus says, “because biology is fundamentally about the single molecule.” The most complicated part of the technology is the optics, which relies on a step-motion camera to take 30,000 pictures of every stage of the process, from adding bases to washing away the fluorescent signal.
While the technology is ironed out at home, Lapidus and his team are out drumming up interest in it. “We’re getting a surprisingly good reception” from oncology departments in big pharma, he says. Throughout, the focus remains on cancer. “That’s the raison d’etre for Helicos,” Lapidus says.
— Meredith Salisbury