In securing the rights to a “third generation” sequencing technology years before it will be ready for market, Sequenom has laid long-term plans for potential diagnostic applications of sequencing, and has also expanded its genotyping toolkit beyond the fine-mapping capabilities of its flagship MassArray technology.
In late September, the company said it had exclusively licensed from Harvard University a single-molecule DNA sequencing technology based on an optical readout method coupled with nanopore arrays. Amit Meller conceived of the technology, which is still at the proof-of-principle stage, while at Harvard. He has since joined Boston University’s department of biomedical engineering as an associate professor.
Sequenom also plans to license additional intellectual property that Meller’s lab has been developing at BU, and is still looking for other technologies that complement the nanopore approach.
“We have been looking at all of the new sequencing technologies as they emerge in the public domain,” says Charles Cantor, Sequenom’s chief scientific officer and a biomedical engineering professor at BU. But since the company’s long-term interest is in diagnostics, that placed a number of constraints on its choice, he says: sample prep had to be simple, the platform had to cater to projects small and large, and it had to be able to reach a low enough price to be practical for diagnostic use.
“It’s not yet clear whether, in diagnostics, you are going to want to sequence whole genomes or selected parts of genomes or just individual genes,” Cantor says. “Clearly, you want to have one platform that scales.”
Also, judging from projects that have used current high-throughput sequencing technologies, “it doesn’t look like they are going to be able to scale to the cost structure that would be needed to make a commercial diagnostic product successful,” he says.
The cost of a diagnostic test, he adds, must not exceed $100 to make it commercially viable, whether what it delivers is a single gene or an entire genome.
But the company sees potential for the technology even in the shorter term. Prior to diagnostic applications, a sequencing platform would give Sequenom an entry point into the growing whole-genome genotyping market. Unlike microarrays, Sequenom’s MassArray technology, which analyzes DNA by mass spectrometry, does not have a high enough throughput for whole-genome scans.
“What we are missing here … at Sequenom is something that is genome-wide,” Cantor says. “And we did not want to go to any of the array technologies, because our experience in trying to get very high-quality data with samples on surfaces has not been terribly rewarding.”
Still, Sequenom is not done shopping yet. While Meller’s technology, which will likely generate relatively short reads, will be applicable to many sequencing applications, it might not be sufficient for whole-genome sequencing that requires assembling short reads across difficult regions, Cantor says. “I am not convinced at this point that a single technology will enable very cost-effective whole-genome sequencing,” he says. “It may have to be done with multiple technologies.”
For that reason, he says, “we are still looking actively at the possibility of in-licensing other methods that would complement the nanopores,” and would help to assemble short reads into the correct haplotypes.