Craig Martin and team will develop device for high purity and low-cost mRNA
AMHERST, Mass. – Craig Martin, professor of chemistry at the University of Massachusetts Amherst, will lead a UMass team that will spend the next three years developing a process that can deliver the quantity and quality of messenger RNA (mRNA) demanded by a new class of medicines, including the COVID vaccines, faster, cheaper and more effectively than any other method. Martin and his colleagues will be joining Wellcome’s R3 program, which seeks to create a global network of “biofoundaries” capable of producing high quality, low-cost mRNA, increasing global access to these new therapies, wherever they’re needed.
Martin whose co-principal investigators include Sarah Perry and Shelly Peyton, both professors of chemical engineering at UMass Amherst, is at the cutting edge of a new approach to medicine. Traditionally, illnesses have been cured by medicines that come from outside the human body: herbs, chemicals and vaccines. Recently, there’s been a new approach, using biologics, or therapies that delivers missing proteins to the human body and which can be used to treat a very wide range of illnesses that result from missing or damaged cell proteins.
But, says, Martin, this process can be taken one step further. “Instead of making the protein in some other organism and delivering it to humans,” he says, “we can make the RNA that encodes the protein, deliver that RNA as the biologic, and the patient’s own cells then make that protein from the delivered RNA.” The result is that, when the body makes the protein itself, “everything gets done correctly.” Furthermore, says Martin, “once you know how to make the RNA for one disease, it’s comparatively easy to swap in a different RNA so it can treat another disease. You don’t have to reinvent the wheel, saving money, and, crucially, saving time.”
If RNA therapies have not yet reached their full potential, it’s because making RNA that is pure enough, in great enough quantities, has proved very difficult—and the purity is of utmost importance. Impure RNA looks, to the body’s immune system like an invader and triggers an immune response. “This is actually ok for vaccines,” says Martin, “because what vaccines do is train the body’s immune system to recognize disease."
For certain diseases, though, especially those that are caused by genetic deficiencies, and for which the immune system plays no role, purity is important. Take cystic fibrosis, for example. Impure RNA would cause swelling in the lungs, making it even harder for a patient to breathe—a potentially deadly complication. Many cancers, too, are the result of genetic malfunctions, and could be treated with RNA therapies.
Martin, whose lab has been studying RNA for more than 30 years, has developed an approach to making RNA that employs a “flow reactor.” This method results in much larger quantities of much purer RNA. It is also scalable and can provide small amounts of RNA that could, for instance, address a particular person’s cancer, as well as the enormous amounts needed for something like a COVID vaccine.
While the Martin and Perry labs have already developed an initial smaller-scale version of their process, Perry and Peyton will help refine the process and be responsible for helping to scale the initial to industrial uses.
“The microfluidic aspects of this technology rely critically on their small size,” Perry says. “Therefore, we will not ‘scale up’ so much as ‘scale out,’ creating many parallel reactors that can operate simultaneously to produce sufficient product for commercial use.”
This scaling out, says Peyton, relies on a series of porous scaffolds, which Perry will engineer. Peyton will incorporate these porous scaffolds into the reactors. “Without both,” she says, “such an ambitious goal of continuous production of long mRNAs would not be possible.”
The work is part of the larger Wellcome Foundation’s Leap Health Breakthrough Network, a web of more than 70 world-class institutions, non-profits and commercial entities representing a network of over 650,000 scientists and engineers across six continents and is supported by a major grant.
Early support for this work was provided by UMass Amherst’s Institute for Applied Life Sciences (IALS), which combines deep and interdisciplinary expertise from 29 departments on the UMass Amherst campus to translate fundamental research into innovations that benefit human health and well-being.