High quality mRNA provides you with results that matter

For most things, the difference between 80% and 90% in quality is marginal. Consider a cookie that’s ~10% better than another or a computer that’s ~10% faster than the next. The difference is not profound. mRNA is different. For mRNA, a 10% difference in quality is the deciding factor between an approved medicine and a delayed program.

mRNA is manufactured through the process of in vitro transcription (IVT). This process uses an enzyme called T7 RNA polymerase. Along with mRNA, this enzyme produces small amounts of a byproduct called double stranded RNA (dsRNA). The human immune system has evolved to detect dsRNA in even tiny quantities. When the immune system senses this impurity, it tells cells to shut down protein synthesis and can even signal a potent immune response. Both effects are counterproductive to the purpose of mRNA medicine: cells make less of the desired protein and trigger more immunogenicity. High quality mRNA is the solution to this challenge.

Terrain is making the world’s highest quality mRNA. 

Making better quality mRNA starts with being able to quantify and minimize these important impurities. Today, most people making and regulating mRNA medicines still rely on the “Dot Blot” assay to measure dsRNA. This assay is not sensitive enough to accurately predict immune response in cells or animals, including humans. There are far better assays that can and should be used. To illustrate this one example, Terrain utilizes an assay that is ~2000x more sensitive than what is currently being used by others and what is being accepted today by regulators.

Beyond simply monitoring impurities, Terrain’s philosophy is to utilize methods that don’t make impurities in the first place. In addition to preventing impurities, Terrain cares about verifying the sequence of your mRNA. We verify it 3 times at various stages of production - including immediately before IVT. This affords confidence that the mRNA requested is the mRNA that you’re testing. After IVT, we verify integrity, not by e-gel, but by using the same capillary electrophoresis methods expected for clinical grade material. Only then do we deliver our high quality mRNA to our partners. 

Quality matters at every step of the process for discovering, developing, and manufacturing mRNA medicines. Achieving high quality only becomes more challenging as you scale. Our mission is to make better mRNA and to give our partners the best chance of success at all stages. Low quality isn’t something that you can figure out later; it’s critical from the earliest stages of R&D all the way to the clinic. Selecting Terrain as your mRNA partner ensures you get the high quality mRNA your research and patients need.

This is the beginning of a larger conversation. Over the next series of posts, we will go into details of how we believe Terrain will change the landscape and improve the chances of translating amazing scientific promises into therapies that meaningfully improves the lives of patients.