Better mRNA medicines might result from Ngo team’s new cell imaging tool
By Patrick L. Kennedy
The inner workings of how genetic messages are decoded inside human cells can now be observed with greater clarity and in real time, a Boston University College of Engineering team has reported in Nature Methods. The researchers’ advances might help us understand how to improve mRNA medicines, making them more affordable, accessible, and applicable across a broader range of diseases.
There are imaging tools that allow researchers to study how complex molecules and nucleic acids move about within a cell, send signals, and produce antibodies. But these existing tools suffer from some limitations. “It’s been much easier to look at proteins,” the final product of the cell’s machinery, says doctoral student Christopher Kuffner, one of the study’s co-authors. “It hasn’t been easy to do that with RNA. This new system allows us to see in unprecedented detail what these molecules are doing.”
Led by John T. Ngo, associate professor of biomedical engineering, the team has engineered coat proteins that bind to RNA when introduced into a cell sample. Upon binding, the proteins light up so as to be seen through a microscope. Crucially, however, the proteins that haven’t found RNA molecules to coat are designed to decay and disappear, eliminating the visual clutter that has plagued previous imaging tools. Coated by the proteins that remain, the RNA molecules clearly stand out in the sample when photographed or recorded in videos of live cells.
“We get really detailed, high-resolution, up-close images, and it works across a lot of different cell lines,” says Ngo. “Just looking at a single molecule, the subtle motions it makes are suggestive of what’s happening—is it being turned into a protein right now? And there are anywhere between hundreds to tens of thousands of these molecules in every single cell. And since we can observe them all simultaneously, that generates an enormous amount of data.”
Ngo, Kuffner, and postdoctoral fellow Alexander Marzilli, who together combine expertise in cell biology, biochemistry, and bioengineering, have made their new method available to other researchers who are making genetic parts and tools to program or study cells. “There’s a lot of potential utility here,” says Ngo. “Researchers can use this tool to study natural processes, to study mRNA-based medicines, and to engineer cells.” Ngo and Kuffner hope to see their work lead to improved therapies for cancer, autoimmune disorders, neurological disorders, and more.
“Cells control mRNAs in lots of very sophisticated ways, and the mRNA medicines developed so far haven’t taken advantage of that,” says Ngo. “What we’ve provided now is a tool to make that more straightforward to do.”