With the astonishing progress in genomics and next-gen sequencing (NGS) over the past two decades, it is little wonder that researchers and entrepreneurs have looked to repeat their success in the complex three-dimensional world of proteins. Of course, proteins contain a vast amount of relevant information that is largely unexplored, especially relative to genomic information.
The emergence of NGS transformed genomics by enabling the analysis of billions of DNA sequences in a single instrument run. But in protein analysis and peptide sequencing, throughput is much more limited. Yet, this protein information is direly needed for a better understanding of proteome dynamics in health and disease and to help enable precision medicine. As such, there is huge interest in developing “next-generation” tools to miniaturize and highly-parallelize collection of this proteomic information.
Who better to tackle this problem than Mark Chee, PhD, and Kevin Gunderson, PhD, of Illumina fame? To do so, they co-founded Encodia, which has been operating in stealth mode since its inception in 2015, to develop new technologies for creating scalable and parallelized approaches to protein analysis. Their goal is to enable breakthrough proteomics research, which is simply not practical or cost-effective using current technologies.
Encodia co-founder and president Mark Chee previously co-founded Illumina and was Director of Genetics Research at Affymetrix. Mark has published scientific papers on microarray technology and applications and is an inventor on over 70 issued patents. Co-founder, vice president, and CTO of Encodia Kevin Gunderson is formerly Senior Director of Advanced Research at Illumina, where he spent the better part of two decades overseeing R&D scientists and projects aimed at developing both DNA array and NGS assays and technologies.
GEN Edge recently interviewed Gunderson to get an early glimpse at Encodia’s plans and underlying technology.
GEN Edge: Please tell us a bit about the mission or values behind Encodia?
Gunderson: In a nutshell, Encodia wants to be to the proteomics field like Illumina was to genomics. My co-founder Mark Chee, who co-founded Illumina, and I was one of the first employees there. We spent many years there scaling genomic technologies and democratizing it. There’s a lot of wonderful tools in genomics. Proteomics, though, is behind in innovation for many reasons. It’s much more challenging to work with proteins than DNA. You’ve seen one DNA, you’ve seen them all! With proteins, it’s a bit different. Mass spec has made a lot of progress over the past ten years, and that’s the main tool for proteomics. There are other tools out there but most of them are antibody-based. Some of those have been coupled with DNA and NGS readouts.
Our goal at Encodia was to democratize proteomics to make it much easier for researchers to do proteomics experiments. Transcriptomics or RNA sequencing has been a surrogate for proteomics for most investigators, and that’s a tool that’s routinely used in NGS. That’s transformed how we do transcriptomics. Researchers do transcriptomics but don’t really delve into proteomics because it’s much more complex. You have to have a collaboration with a mass spec lab, and it’s not easy.
We wanted to bridge that gap, make it easy for a researcher that’s doing transcriptomics to move over and do the proteomics assay all in the same type of data. We wanted to continue to use an NGS data type that researchers are used to processing and do it on NGS sequencers that are now widely distributed. There’s a wide availability of NGS sequencing and a lot of new NGS technologies coming online. We want to ride that wave of NGS.
That’s the mission of the company—to democratize proteomics and make it widely available and easily accessible. We want to ride the technology wave of NGS because that’ll be continually improving higher throughputs. Hopefully, sequencing costs keep going down, and we’ll just ride that wave right.
Ultimately, we are doing an NGS readout. We have patent publications that started to describe a lot of the technologies. We’re basically reverse translating proteins back into a DNA code that you can then read out on NGS. That’s the heart of our technology. Biology goes from DNA to RNA to protein. We take it backwards in a massively parallel, innovative way. That allows the user to really focus on doing proteo-genomics. We expect our user base to be doing genomics and transcriptomics. Now we want to throw in the proteomics as well and then integrate all that data to get a full picture of the biology.
GEN Edge: DNA is a linear code but when we talk about proteins, we start moving into three-dimensional structures. I imagine you want to get to where you can look at protein modifications and all the stuff that comes along with the protein world?
Gunderson: We plan on doing that over time. We’re starting with determining the linear sequence of proteins, mapping them, and quantifying proteins. Then there are post-translational modifications. There’s proteo-forms, the combinations of the post-translational modifications and variance on a given protein. That will be a continual evolution of a product. There’s a lot of complexity, and understanding that complexity is where all the action is at.
GEN Edge: How does being dependent on or choosing to ride NGS help or limit the company?
Gunderson: There are hundreds of millions, probably billions of dollars being put into NGS research innovation. There are more companies entering that space. So we think that’s a good space to be in and want to ride that wave. We don’t see any issue with that entering the marketplace if these machines have proliferated, which they have been done. It’s a low barrier to entry rather than if you’re selling a very expensive specialized instrument, which is a huge barrier to entry. We think we’ll have a much lower barrier to entry, allowing us to get customers all over the country and all over the world. Nowadays, everybody has access to NGS. A lot of core labs and a lot of research institutions have it. It’s becoming pretty common. I think that’s a key advantage of our approach and don’t see any downside. Mass spec is a great technology that will still be around. It’s a beautiful technology as well. And I think we will be complimentary to mass spec in many ways.
GEN Edge: Will this technology be compatible with doing multi-omics experiments?
Gunderson: Certainly. Investigators can run their transcriptomics and proteomics all in one fell swoop. The multi-omics and proteo-genomics—that’s where we want to be, supporting that kind of activity.
GEN Edge: Now you can go from investigating a genomic sequence, looking at variants, and seeing how the proteins are affected in one fell swoop?
Gunderson: Yes. You’ll have information on expression quantitative trait loci (EQTL) and protein quantitative trait loci. All that information should be there.
GEN Edge: Are there any hypothetical situations you’d want to see the technology applied to?
Gunderson: In the long run, we’d like to be able to see a patient go into the clinic and get their blood sample taken and then get a full proteomic profile that predicts their apparent state of health or disease and what organ systems are failing. Do you have heart failure, kidney dysfunction, liver issues, or Alzheimer’s disease as seen from biomarkers in blood?
Potentially, you can monitor the entire physiologic state of a patient just looking at proteins in the blood because the blood interacts with practically all the tissues in your body. So, it actually reports back dysfunction and cell death in certain places. There’s a lot of information there, it just can’t currently be read out very effectively. Our goal is to be able to read out all those markers of state of health and disease. That should help doctors treat patients in the long run.
GEN Edge: What has it been like working across many scientific disciplines to solve this problem?
Gunderson: We have used the matrix approach and had project teams. We create cross-functional teams with many different skill sets. It’s fun working with all the different disciplines. You have to trust everyone who’s an expert in the other field. They bring their expertise to solving difficult problems, and then we help put it all together. It’s been a lot of fun learning a lot of new technology areas that I hadn’t really explored before. But we know the principles of how you put together scalable assays and technologies and teams.
GEN Edge: How has this endeavor been different from Illumina, and what have you learned from that experience that’s helping with Encodia?
Gunderson: The startup environment is different now than with Illumina. Illumina is a very special case. It probably doesn’t come around very often. When I started there, we went from seven people when I joined to an IPO within a year and a half. This was at the end of the “dot-com” bust. We just got in at the end of that window, which closed very rapidly. That was a very fast ride.
Nowadays, I would say it takes a lot longer to get to that point. You’ve got to show that you have a product and revenue. Back in the day with the “dot-com” era, it was a bit crazy. But Illumina was the beneficiary at that point of a nice IPO that allowed us to develop a lot of technologies and do some pivots along the way.
This time around it’s a bit different. Proteins are more challenging than DNA. We mapped out a lot of things on paper, but I would say reducing the practice at some level, it takes a lot of work, it requires a lot more disciplines too. We do a lot of assay development, protein engineering, chemistry, engineering, bioinformatics. It’s been a great challenge, a new challenge for me. I spent 18, 20 years doing genomics basically before co-founding Encodia.
GEN Edge: How has the recent funding climate influenced the company, the direction that you’re going, and how you manage the growth of the company?
Gunderson: The funding environment has been good and supportive. It hasn’t been crazy, it’s been realistic. We’ve been able to raise funds. The community is excited about the technology. I think everyone realizes proteomics is an area ripe for innovation and new approaches. As genomics is maturing, there’s a lot of researchers interested in proteins. Protein is where all the action is at. Genomics gives you a lot of predictability and probabilities. But to tell you the actual state of affairs of a biological system, you’ve really got to look into the proteins. Whether you want to look at human health and disease, DNA analysis gets you a lot, but you really need to know the current state of affairs. You get that from proteomics.
Every time you go into the clinic, typically you get a protein or a functional test, not so much a DNA test, because proteins tell you the here and now what’s going on. It’s a missing piece right now in terms of ‘omics technologies.
GEN Edge: Where do you hope the company will be in a year, five years, in 10 years? What does the trajectory look like?
Gunderson: The next era will be for attracting great employees, get people excited about the potential, and what it can do in research and human health. Hopefully, in a year we’ll actually be launching products to customers and getting those into the marketplace. That’ll be exciting—getting your first product into the market, interacting with customers and figuring that out.
Longer-term, we want to expand our applications, have a dialogue with customers and key opinion leaders. Then in five years, we want to permeate the market. If you’re going to do a protein assay, I want them to think about using our platform and integrating their data sets with transcriptomics. I hope to see good market penetration and use across most research groups. It may not be in the clinic yet because that takes longer, but certainly for a lot of the academic researchers and clinical researchers at the research level.
A decade out, I hope we’ve transformed into a larger company that has a real presence in research and we have clinical assays under development. Those could change dramatically from what we’re doing today—in a decade there are new ideas that come along, you hire a lot of people, a lot of things can happen. But in general, I want to see our company impacting human health.
Jonathan Grinstein, PhD, is a freelance writer and GEN Edge contributor based in San Diego.