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Q&A: SciLifeLab's Ulf Landegren on Commercializing Multiplexing Technologies

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ulf2.jpgName: Ulf Landegren

Title: Professor, department of immunology, genetics, and pathology and SciLifeLab, Uppsala University

For a person who has spent the majority of his life in academia, Ulf Landegren seems to have a keen business sense. To date, four companies — ParAllele Bioscience (now part of Affymetrix), Halo Genomics (now part of Agilent Technologies), Olink Bioscience, and Q-linea — were founded on IP related to multiplexing technologies developed in Landegren's laboratory at Uppsala University. In addition, he maintains that many of the opportunities contained in IP licensed to Olink, the Uppsala. Sweden-based firm Landegren co-founded in 2004, have not yet been realized.

According to Landegren, the secret to generating a reliable stream of lucrative technologies lies in reusing basic ideas about probing and multiplexing.
While he has seen many of these multiplexing technologies reach the market successfully, he said that there are still obstacles to commercializing them, especially in Europe, where researchers are less eager to try new platforms, and venture capital companies lack the experience of their American counterparts.

However, he said that Sweden's Science for Life Laboratory, a national life science infrastructure created in 2010 around academic resources in Stockholm and Uppsala, has given technology developers the ability to make their new platforms available to more local researchers.

BioArray News spoke with Landegren during a visit to Uppsala last week. Below is an edited transcript of that interview.


When did your career begin in terms of technology innovation and platform development?

Well, it depends on how far back you want to go. I had a rather early start in science. I was lucky enough to have my own lab when I was 19 years old, by chance. I got a job as a technician's assistant, but it turned out that there was no technician to assist. The person who was running the lab was more interested in teaching. So I had a budget and a facility in the genetics department at the Swedish University of Agricultural Sciences.

Did you know what you were doing?

I think so. I developed some genetic markers for agricultural and plant research, and published a paper. But then I went off to medical school and studied immunology. And then I went to California Institute of Technology, where it was very apparent that the future way of working in biotechnology was to take things as far as you could in academia and then transfer them to a company. That wasn't at all the mindset in Uppsala at that time. I was there [at CalTech] between 1984 and 1989 and developed the oligonucleotide ligation assay, which was one of the very first genotyping assays. I returned to Uppsala in 1989.

Initially, I didn't have an interest in commercializing anything because I was working with Pharmacia Biotech, [which] commercialized one of our technologies — it was a sample handling technique. We sometimes kick ourselves and say, 'We could have been the next Qiagen,' but [Pharmacia] eventually spun it out with Eurona ... [and] used it as a front-end to its sequencing platform. After [spinning out], Eurona transformed itself into a genetic discovery company, but was probably too early, so it failed. Then it fused with Gemini Genomics, and eventually Sequenom bought Gemini and [Eurona]. And now that technology is completely forgotten.

I started thinking that things might go better if I tried to get a company off the ground on my own. We had been doing a lot of multiplex typing, and other people were involved in single-plex genotyping, so I thought we had a head start. We were approached by people in Stanford University who set up ParAllele Bioscience. I think they did a great job. At that stage, we never would have been able to raise that amount of money in Sweden, and they had all the contacts. It was done very quickly.

We had other things going on. Patents had accumulated and so forth ... so some of my PhD students and two industrialists and I got together and founded Olink. The proceeds from the sale of ParAllele became the startup funding for Olink. But Olink wasn't a very focused company early on because it had a lot of different IP.

Halo Genomics and Q-linea are based on IP from Olink.

And there [are] a number of other things that we can do [with the IP], and the discussion has been: do we do that inside Olink or outside Olink? It is the European sickness of biotech. Everything grows to the size of 25 people at best, and then it either closes down or it is sold to a US company. Nothing gets to grow very large. Olink is capable of taking advantage of a very large [IP] portfolio. We have licensed it to a number of other large companies [such as Affymetrix and Life Technologies].

What kinds of opportunities are you talking about?

Both in genomics and proteomics, I think there is a lot that can be done. Recently, we have developed some new techniques that I am very excited about. But all of the pieces need to fit together.

Why have you devoted yourself to developing these technologies? Is it driven by a perceived need or you felt you just had a knack for doing it?

I think we have some basic ideas that we have been able to reuse in different contexts. We have been developing some completely different techniques, too, but the things that have been successfully commercialized have all been around probing and multiplexing. It was obvious that you need to genotype in multiplex, so padlock probes became a solution to that. Once we could do that, we wanted to do something similar for proteins, and then proximity ligation came as a consequence. I had been looking for a way to implement for proteins some of the mechanisms we use in DNA analyses — dual- or multiple-recognition and amplificationof the response. Some of our newer technologies are still in the same area. They are new ways of probing in a way that can be multiplexed.

What are you working on now? Are you advancing the Olink technology further?

I think for Olink it would be good to have even higher sensitivity … and to get a very steady stream of high-quality reagents and convert them to assays. That is something my lab is doing together with Olink.

Genotyping by sequencing is an increasingly popular application. There are other companies developing new technologies. What do you think the next generation of genotyping will be? Will interest in these other technologies plateau?

I don't see a plateau. I just think that next-generation sequencing has received all the attention. One recent interesting development is by my colleague Mats Nilsson, who is doing in situ genotyping and sequencing. He published that in Nature Methods in August. He demonstrated that he can genotype transcripts in situ either by sequencing the transcripts or he can sequence tags, which allows him to distinguish theoretically a thousand different transcripts. Regular sequencing in situ has received a great deal of interest because of the way diagnostics work. Pathologists are more familiar with microscope-based visualization than PCR. The pathologists want to get as much info as possible from the microscope. If they can get the genotype by the microscope that would be very attractive for them, so I think there is a good chance that the method will be commercialized.

How has the creation of SciLifeLab benefited your work?

I think SciLifeLab is a different thing to different people. It serves to establish a minimal level of technical competence accessible for all. Technologies that are a bit expensive can now be made available to more people. But I think we need to look for unique things that we can do better than anyone else, and I think we should try to scale those techniques up to generate new biological data sets. One big difference between technology development in Europe and the US is that there are many more early adopters in the US. There is a whole group of people in the US that is eager to latch on to new technologies. In Europe, we are very strong on technology innovation but we often fail in capitalizing on it. The first next-generation sequencing platforms were developed in Europe but all of the commercialization was done in the US. Also, earlier, with microarray technology, much of the early innovation was done in Europe.

Are you referring to Sir Ed?

Sir EdwinSouthern was certainly one of them. There were a lot of innovators. Also, Radoje Drmanic, the founder of Complete Genomics. So we have been very poor at capitalizing on new technologies, and my hope is that SciLifeLab will help us take technologies a bit farther by making them available more broadly locally before we send them over the ocean. We also have the Human Protein Atlas project here, and I think that also helps us build resources, but we have to do the job of making them more widely available.

What are other factors impacting the commercialization of these technologies in Europe?

Another factor people bring up is the paucity of venture capital — that is a problem. But I think that it's more an issue of having competent venture capital. The VCs on the US West Coast are so much more experienced than those in Sweden and Europe in general.

Still, to date there are four companies that have been spun out from your lab.

That's correct. ParAllele was acquired by Affymetrix and Halo was acquired by Agilent Technologies. They have completed their journeys quite successfully. Olink is still in build-up phase, but it is doing pretty good, and Q-linea is a bit earlier in the process, but also doing well with interesting prospects.

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