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This article was originally published by the UMass News Office.

Craig Martin, professor of chemistry, and Sarah Perry, associate professor of chemical engineering, both at the University of Massachusetts Amherst, recently received support from the National Institutes of Health (NIH) to develop a novel approach toward efficiently, reliably and cost effectively synthesizing novel strands of specialty “long RNA.” Future genetic research into everything from basic cell biology to advanced therapeutics depends in part on having just the sort of complex, modified RNA that Martin and Perry will be working to make widely available.

RNA is a molecule that is in all living cells and plays a role in nearly all biological processes, including carrying instructions for making proteins and turning genes on and off. While RNA was discovered over a century ago, researchers are still uncovering new RNA-related pathways and RNA structures. Recent scientific advances have harnessed RNA to develop technologies and therapeutics such as small interfering RNA-based drugs and messenger RNA-based vaccines against cancers and infectious diseases.

RNA is composed of thousands of bases, and, like DNA, RNA has four of them: A, C and G, but, instead of DNA’s T, RNA has the base U. Each of these bases can be further “decorated” with various specific chemical modifications in particular places to tell the RNA how to build, and control the building of, increasingly complex proteins. “For more than three decades, my lab has been studying the enzyme that is now used to synthesize RNA therapeutics, like the COVID vaccine,” says Martin. “But current synthetic systems are unable to generate RNA with these complex modifications, slowing research in this exciting new area.”

Having a reliable, cost-effective supply of long, modified RNA is the first step in doing this advanced research—which is where Perry comes in. “As a chemical engineer, I help to design the process for manufacturing RNA. I make microscale devices—think of a complex chemical refinery, but with equipment that is the size of a human hair. My lab is inventing the machines that will be able to automatically generate long, modified RNA.”

“A deeper understanding of RNA and its potential applications can advance our knowledge of living systems and can have profound impacts on human health.” said Carolyn Hutter, director of the Division of Genome Sciences at the National Human Genome Research Institute, part of the NIH.

RNA can also be synthesized chemically, which works well for RNA with 30 or 60 bases, but it can’t generate RNA when hundreds or thousands of bases are involved. Martin and Perry will instead rely on a natural enzyme, known as RNA polymerase, with their mechanical automation of the RNA-generating process. 

“The enzyme is a much better chemist than humans are,” says Martin. “If we can leverage its sophistication and efficiency in the machine Perry is building, then we hope we’ll be able to provide the source material that will allow scientists to dramatically enhance our understanding of RNA in biology.”

Article posted in Research