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NC State s Len van Zyl Preps Another Triangle Microarray Firm

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At A Glance

  • Len van Zyl (pronounced von sail)
  • Title: research assistant professor, forest biotechnology group, NC State University.
  • Education
    • 1992, BSc, Biology, University of the Orange Free State, South Africa
    • 1995 — MSc, University of the Orange Free State, South Africa.
    • 1999 — PhD, (Unesco Center for Microbiology and Biochemistry) University of the Orange Free State, University of Pretoria.
    • 1999 — Postdoc , North Carolina State University, biotechnology.

If there were any doubt, here is another reason why the Research Triangle area of North Carolina is rapidly positioning itself as the North American nexus for microarray analysis.

The newest player to join a rapidly growing troupe is ArrayXpress, a firm growing out of NC State, based on microarray analysis techniques developed by Len van Zyl, a 33-year-old assistant professor in the school’s forest biotechnology group.

ArrayXpress joins Research Triangle Park-based Paradigm Genetics, which recently introduced a microarray analysis service based on the Agilent platform, and Expression Analysis of Durham, which conducts assays on the Affymetrix platform, as commercial providers of sample-to-data analysis. These new services, appearing like dandelions on a spring lawn, exist alongside of the microarray core facilities already in place at the three area universities — Duke, the University of North Carolina, and NC State.

Van Zyl, who was an investigator on the just completed multi-million dollar NSF research project on the pine genome, promises that he won’t give up his research work just yet. However, the research assistant professor is deeply involved in the start-up planning for the company, which is being incubated by an agency in the university created to nuture just such young companies coming out of biotechnology research efforts at the land grant college, long respected for its agricultural research.

ArrayXpress has retained CEO Michael Zapata III, a serial technology entrepreneur who flies Apache helicopters in the North Carolina Air National Guard, and CFO Jon Woodall, who left a well-established career as a partner one of the Big 5 accounting firms, to guide the new company.

BioArray News spoke with van Zyl to learn about his technology innovations and the newest microarray analysis player hitting the Research Triangle stage.

How did you get involved in microarrays?

When I started here in 1999 as a postdoc, we were applying for a grant to the NSF for [sequencing] the wood-formation genes in the pine genome. We were successful in getting the grant [a $4.8 million multiyear funding that ended in February] and there was a huge sequencing activity here. [As part of the postdoc] I went to Sweden, where we had collaboration with the Swedish University of Agriculture. They were very inter-ested in the Norway spruce and wanted to see if we could use the pine genome for comparative analysis of genes involved in lignin or wood formation in spruce. I went there and we started doing microarrays on a macroarray scale.

That’s how I got bitten by the bug. When I got back, I was very lucky to be appointed [to the NC State faculty].

I started working on spotted arrays on glass in the middle of 2000. I started to play and see what you could do to develop a technology that will be very reliable for everybody to use.

I basically took all the procedures that I could find on the Internet, and combined them with the work I had done using the macroarrays. And, just by pure luck, I stumbled on something that worked so incredibly robustly that anyone could do it. We have utilized the process repeatedly, and consistently. The results have been superior.

So, you have developed some new techniques?

It’s a optimized procedure based on a Cy3 and a Cy5 labeling strategy. I played around with different procedures and protocols and got a novel procedure. It is in some part an optimized procedure in order to reduce background and provide superior quality data. I came up with a tool that can, by more than 50 percent, reduce the cost of labeling. But, I didn’t think this was such a big issue until the university started to see the response of people towards this. They asked me to submit it for a patent. It’s not a novel technology, just a novel procedure that is really so robust that you can’t go wrong with it. There is excellent signal-to-noise ratio, and zero background.

How did you get the idea to create a company?

Certain large commercial organizations focused on molecular biology signed confidentiality agreements to look into this for the university. At one stage, they told me that I had to be faking the data. I told them, “come on, you can work with me in the lab” One of the VP’s for technology came here and looked and said he just couldnot believe it. I realized there was an opportunity there. We incorporated in January 2003. But, I’m a scientist and I’m from South Africa. I realized that I was completely out of what was going on here. That’s where I started to see people and grouped up with the TEC Program at the university, which was developed to assist scientists, specifically technologists, spin off startup companies. The program, for which the university got an NSF grant, puts you in contact with people you might want to hire as CEO, as well as lawyers, and accountants.

Through that program, I got my CEO, Michael Zapata, who is the CEO of several other companies out there. But he is really focused now with his main priority being ArrayXpress. I have a really great business team that is now 10 people strong.

What are you doing for lab space?

The good thing is the building that we are currently in [on NC State’s new Centennial campus], there is the EDC, the entrepreneurial development center. They have lab space upstairs, directly above my lab, and we are considering moving in there. I would be very comfortable for me; I would just have to go upstairs to my office.

At what stage is the patent process?

The University and I have previously filed for two US provisional patents. We are currently working on patent related issues with North Carolina State Univer-sity’s office of technology transfer. The main emphasis for the company is that we will sell data, we will not sell chips or anything. The platform is cDNA arrays or spotted oligo arrays, depending on what the customer wants. Currently, people are asking for 70-mer oligos.

Why do you think you can succeed?

I have been through the idea so many times, struggling with it. I have looked through the market and tried to see where the gaps are. I saw an opportunity, and I hope that it is still an opportunity, to provide a complete start-to-finish microarray solution. We plan on focusing on the agricultural part of the market and work on non-model species like sweet potatoes, corn, tomatoes, rice, and also on pathosystems.

Another possible market is textiles where micro-arrays can be used to identify genes that are involved in natural fiber production.

One of the larger thrusts behind this is that you can provide small targeted arrays, and focus in on specific genes that have been identified using other systems.

How are you going to provide analysis?

We are in the final stages of negotiations with SAS Institute for purchasing the SAS microarray solution software. I’ve been working right from the beginning with Russ Wolfinger [SAS director of genomics] in helping to evaluate the SAS microarray software system.

How about the experiment design?

We will sit down with the customers and design an experiment according to the questions the customer wants to address, with the use of the PhD-level statisticians. After we design the experiment, they will send us a tissue sample, we will extract the RNA. Or, they can extract the RNA and send it to us, but there are certain requirements for that, as quality is extremely important. We will do the extractions, the labeling — using what-ever strategy, either my protected technology or amino allyl, whatever commercial system is available — as well as all of the hybridization, the scanning and provide a complete data analysis. The main emphasis, for me, is the quality of the arrays.

How will you fund this?

We have one contract signed with a company in the agricultural sector. With another company, we are negotiating a multi-year contract based on performance. I can not say the names. But, we start off revenue-positive, and we have decided that we are not going to dilute the company with venture capital, yet. The companies will pay some money up front so that we can buy the equipment. We will buy a relatively high-throughput robotics system, an automated hybridization system, and everything will be more or less automated.

What kind of capacity do you think you can achieve?

We think we can do 5,000-plus arrays a year, easily. I want to start with small sure steps and not let things get out of control. I don’t just jump into things and I’ve pondered this a while. In Afrikaans, there is a saying: “Jy kyk die kat uit die boom.” (“You watch the cat in the tree to see what he is going to do next”). I have no illusions that this could fall flat. But, I believe that it’s a good idea and is needed in the market. Our company will provide the client a complete microarray solution, to allow the scientist to focus on the relevant biological issues.

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