RNA is a powerful, versatile molecule
This week’s Q&A features Cofactor Genomic’s COO, Dave Messina. Dave talks about the innovation in RNA including current uses, like creating a pest resistant type of corn. He also looks to the future with RNA therapies and discusses major challenges facing this approach.
Q: Chemical and Engineering News recently asked, “Is this the decade of RNA?” What did they mean?
A: RNA is having a bit of a moment lately and it’s really not surprising considering how versatile of a molecule it is. RNA occupies a sweet spot in between DNA and protein. Proteins are really what do all the work in the cell but they’re very hard to work with in the laboratory, so we can’t really directly access proteins as effectively as we would like. DNA on the other hand, is very easy to manipulate in a high throughput and very effective way, but tells us very limited information about what’s actually going on in the cell. RNA is the sweet spot in between where we are able to access the information we want using tools that have been developed for DNA. Because RNA is so versatile, it’s no surprise that it’s being used in all sorts of different methods and applications today. RNA interference uses RNA to bind to another RNA and block its activity. There are ways of using small molecules in the same way that will bind to a specific RNA and prevent it from being translated and made in a protein. Then you have RNA being developed as therapies as well.
Q: What do you think are some of the major challenges of RNA therapies?
A: RNA as therapy is an exciting area and there’s lots of potential and cool things going on there but there are some challenges. First, RNA is transient so it’s designed not to hang around for very long. If you want something stable, that’s what DNA is for. Making RNA into a stable molecule that you’d need for a drug is challenging. RNA is also quite large, floppy, and thick in structure, and thousands of bases long. It presents a challenge because you’ve got to make that enzymatically, so doing that consistently is the difficult. You also have its ability to provoke an immune response so the body may see that as a foreign body and you need to make sure that it’s protected from that. All those things together mean that there is a challenge in delivering RNA’s as a therapy and the primary way that is done today is with nanoparticles that you need to encapsulate and wrap up. There’s a lot of tremendous work that’s being done in this area but definitely a lot of work still to be done in order to make a make RNA therapies more mainstream.
Q: What about RNA in agriculture? Are there applications in there?
A: Absolutely. About 18 months ago the FDA approved the first RNA-based pesticides for use in corn. How did this work? They actually work using RNA interference. There is an RNA that’s specific to this pest, the root worm, and the pesticide is being made by the plant itself. When the root worm ingests that RNA, it causes an RNA interference reaction to happen and it blocks a vital RNA in the root worm, so blocking that vital RNA prevents a critical protein from being made and the worm will fail to thrive as a result. This is really interesting application and because it’s specific to that worm, it’s a very safe and effective way of having the pesticide built in to the plant and making sure that there is a healthy corn crop.
Q: Does any of this apply to Cofactor? How do you use RNA?
A: So we’re talking about how RNA is a such a versatile molecule and at Cofactor we use RNA in yet a different way. We use it as a diagnostic assay for cancer. There is this amazing new class of anticancer drugs called immunotherapies and they use the body’s own immune system to fight the cancer. When they work, they work really well but they only work on average about 30 percent of the time. They also tend to be quite expensive, as much as $150,000 per patient per year. Wouldn’t it be great if the physician knew ahead of time whether prescribing that immunotherapy to a given patient would actually be helpful to that patient or whether a different therapy might work better? That’s where our assay comes in. By combining RNA signals which we gather from the patient’s specific tumor with multi-dimensional models that we’ve built that model the immune system and how it’s functioning inside a tumor, we can predict whether a given patient is likely to respond to therapy. We can then give a readout as to which drug is likely to be most effective for that specific patient. It’s another great way to apply RNA to make sure that patients get the right drug the first time and that we’ll be able to help them.
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