Cofactor Genomics: Leveraging the power of RNA
We get hung up on the genome a lot here at Front Line Genomics (the clue is in the name). But in reality the genome is just one component of a broad swathe of molecules that can be leveraged to better understand and treat disease.
One of those molecules is RNA, which has enormous potential as a means to understand disease from diagnosis through to treatment and even monitoring. To better understand just how RNA can be used to make personalised medicine a reality, we sat down with Jon Armstrong, CSO of Cofactor Genomics. Cofactor is using RNA to diagnose disease, from discovery through to clinical assays, and will actually be launching their first diagnostic assay, an RNA-based biomarker panel for cancer, later this year.
Thank you for taking the time to speak with us. First, could you tell us about Cofactor Genomics, and what the company is hoping to achieve?
The founders of Cofactor were all together at the Washington University Genome Institute. We started the company to bring sequencing to the masses. At that time, sequencing was mostly performed at institutes or large genome centres. Over time we’ve developed a lot of strong partnerships with academic and pharma clients, and 4-5 years ago we began to focus our efforts on RNA. We’re making a concerted effort to better understand RNA as a molecule and how the attributes of RNA can be leveraged for not only discovery sciences, but also clinical sciences.
When Cofactor started, we offered full-service partnerships with people, where we would go from the beginning of process – taking in tissue samples – all the way through to analysis, and we continue to do that now. In addition, we also concentrate on bringing the expertise we have developed with RNA over the past years to both our service partnerships and the development of clinical assays. Our goal is to move RNA sequencing and RNA, the molecule, from discovery to diagnostics. We will leverage the power of RNA as a diagnostic tool for disease.
What are the benefits of applying RNA-seq in a clinical context?
One of the biggest advantages of RNA is that it’s dynamic, and it changes in real time based on the state of an organism. That could be disease, health, nutrition, stress, or others. This trait is powerful because it enables this idea of monitoring for early disease detection. We haven’t really been able to tap this so far, with the exception of some uses of cell-free DNA. RNA with its dynamic, real-time capabilities has the potential to provide monitoring for the early detection of disease as well as longitudinal monitoring after treatment. The dynamic nature, and thus, real-time information, is an extremely important component of what makes RNA a great molecule for diagnostics.
I’d also say that RNA is extremely important because it sits at the intersection of DNA and proteins and we can use RNA to either validate or invalidate features in the DNA. We’re already doing that now at Cofactor, by looking at the expression of RNA in the context of fusion information in the DNA, to understand which fusions are being expressed or not. We’re finding the RNA information to be extremely valuable and orthogonal to the information in DNA. Also, taking into account some of the advances we’re seeing with stabilisation of biomolecules in fluids, I think RNA is a wonderful candidate for non-invasive testing as well.
Where are the biggest challenges in making these tests a regular part of clinical practice, and are there particular hurdles that you’re going to have to overcome?
Big surprise, oftentimes some of the biggest weakness of a molecule are also some of its biggest strengths. One of the things about RNA, where we have built expertise, is it’s lability in contrast to DNA. You have to have a lot of expertise in handling and working with the molecule. That’s fairly minor, but one that’s not so minor is the dynamic component of RNA. As well as being a strength, this is also one of the challenges. With DNA you have two copies per cell, and we have a handle on the dynamism it possesses. But RNA changes, so trying to understand those changes and their relation to disease is a big challenge.
We are developing new technologies and methods and really trying to drive the forefront of these studies. Because these are new technologies and methods, we have to validate them. We’ve already received CLIA and CAP accreditation for RNA sequencing and are driving towards CLIA and CAP accreditation for our clinical assays as well. So, when you are moving forward and are on the forefront of these things, there are challenges that you don’t even know exist! We get excited about uncovering those challenges and being able to get over those hurdles.
We want to make sure to build trust among the community of researchers and pharma that want to have access to our technologies. The way that we do that is by having really good experimental design and intelligent analytical validations, and being very cogent about the way we are validating and proving that the methods we use are sensitive and specific, and valuable to the community.
Where do you see Cofactor going in the future?
We will have our first clinical assay coming online in the fall – Cofactor Pinnacle – and will continue to develop and roll out additional clinical assays over the next several years. In the near future we will be seen as a clinical assay and diagnostic company, which will allow us to continue to expand our partnerships with pharma.
One thing that I think is really great is from our humble beginnings in our first office in St. Louis that was only 1500 square feet, we have become a multi-site company. We have offices in San Francisco, I’m based in San Diego, and we have our headquarters in St Louis where our processing labs are. We will be continuing to grow, driving diagnostic partnerships with pharma, and evolving clinical assays.
Cofactor will be attending Festival of Genomics California in San Diego in September. What will you be sharing with Festival attendees?
I love the conversations that are had at these events; at the pool, at the bar, sometimes in a hallway, someone will say one or two sentences, and you’ll ask “oh, tell me more about that”, or “explain to me what you mean by that”, and you come away with these snippets of information that you probably wouldn’t have picked up anywhere else, only at that place and time. So for me those types of scientific geek-out conversations are the thing that I love to get involved with, especially if they’re about RNA! And there are a lot of really knowledgeable RNA experts that I’ve come across in San Diego, so I’d love to be able to meet and talk with translational RNA people about how Cofactor might be able to help them.
Also, we’re looking for partners for the beta testing we’re doing with our newest clinical assays right now, and it will be great to have conversations with potential partners for this.
Finally, we’ve done an enormous amount of work in the last two to three years on low-input RNA sequencing, and we will have information at the Festival about our low-input RNA solution. We want to help people understand that if you “only” have 500ng of RNA it’s not true that you can’t do anything with it. In fact, I would say that only 500pg is what we’re used to dealing with on the low input side. I would love to chat with people about that if they would like to know more.
Jon and the team from Cofactor will be on site at Festival of Genomics California, and would love to meet with you to discuss everything from low input sequencing to RNA clinical assays. There might even be some “science geek-out” conversations! For more information and to arrange a meeting, sign up here https://cofactorgenomics.com/fog-california
There will also be more information on Cofactor’s picoRNA sequencing and analysis product available in the Transcriptomics session at the Festival itself.