Sequenom’s Eye on the Future

Nov. 13, 2007 | For much of the past year or two, Sequenom has been making headlines for all the wrong reasons, flirting with delisting from the NASDAQ exchange. But recently the mass spec analysis company has rebounded strongly, its share price jumping above $8. In September, news came that the company is looking to commercialize nanopore technology. According to president and CEO Harry Stylli, “Long term, we believe it has the potential to provide a commercially viable, rapid, sub-thousand dollar human genome sequencing solution.”

Bio•IT World Editor-in-Chief Kevin Davies asked Sequenom CSO Charles Cantor about the firm’s recovery and future plans.

Bio-IT World: So how is Sequenom doing these days?
Well, we’re doing much better — our performance both in terms of revenue and on the market clearly shows this. We have bounced back.

What do you attribute that to?
Well, I think we got serious, and really improved our product and made it much more reliable and broadened the range of applications. We have a lot of happy customers now, and a couple of years ago we had many unhappy customers! People have used the Sequenom platform for genotyping, for quantitative gene expression, for methylation measurements. We’re about to launch a product for bacterial and viral identification. So it’s not just a SNP platform now.

Where does the interest in nanopore sequencing come from? Is this just one of several long-range technologies you’re exploring?
It’s not the only future technology we’re looking at, but it’s one I’m very attracted by. Technology is not static, OK? The mass spec is great for studies of a relatively limited number of markers on large numbers of samples. We think our sweet spot is 100 to 1,000 loci — whether they be SNPs, expression, methylation, it doesn’t matter — anywhere from hundreds of samples to tens of thousands of samples. That’s what our customers use our platform for. But the mass spec is not competitive today where you have to look at larger numbers of markers simultaneously.

And of course, some array companies have 1 million SNPs on a single array...
Exactly. So the way I’m viewing the nanopores from the 60,000 feet level is, I think I can use them as virtual arrays. So that I would be able to get the same density of information out of them that you can with the arrays, but I have the tremendous advantage that everything is in homogenous solution. Sometimes nucleic acids work better in homogeneous solution; they don’t like to be on silicon surfaces.

So you’re not necessarily looking at this as a sequencing technology per se?
 That’s correct, I’m looking at it as a broad enabling platform for all kinds of things. Just as the mass spec is a broad enabling platform for all kinds of things. We do sequencing on the mass spec too — that’s how we do methylation. To me it was intellectually a very good fit. It has homogeneous input, no surfaces — and the major challenge on the output side is very fast data processing — digital signal processing, which we’re good at. We analyze our mass spec data on the fly, and we think the nanopore data’s going to have to be analyzed on the fly for optimum use.

Who have you partnered with and what are the next steps?
We licensed the technology from Boston University and Harvard. Our academic partner is Amit Meller, who developed this approach while at Harvard, he is now in the engineering school at BU. Meller was a postdoctoral fellow with Dan Branton (Harvard). Branton was the first person to get the nanopores to work, to visualize DNA molecules. The focus of that lab has largely been on electrical detection. Amit is an optical physicist, who transitioned that platform from electrical detection to optical detection.

How will this be developed?
Our intent is to move forward aggressively, by collaborating with people externally and in house. The long-range plan of course is to develop a mature platform for DNA sequencing. My guess at the moment is that other applications will come quicker...  I view this as a 3rd generation system. I think it’s a broad enabling platform, and I think it may be a faster route to market for genotyping and gene expression than it is for sequencing. The example I’ll give you is the arrays are very good for most things, but very few people are using arrays to try to do sequencing. The way I view these nanopores is virtual arrays, so it’s the same kind of argument.

Do you think nanopores could eventually become a viable 3rd-generation sequencing platform?
Oh, I think they’re potentially revolutionary for sequencing, and we plan to develop them for sequencing, don’t get me wrong! But if I ask how long will it take to have a commercial sequencing platform that I can sell as opposed to how long will it take to have a nanopore that’s not quite as demanding as whole-genome sequencing, then the answer is, I bet the first products will be more limited than nanopore sequencing.

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