Researchers at Chalmers University of Technology in Sweden and collaborators created a technique to produce fluorescently labeled mRNA, allowing them to track its entry and distribution into cells. Using such molecules could help scientists develop better ways to deliver mRNA therapeutics into the body, potentially playing a vital role in the new wave of mRNA therapies, including vaccines.
mRNA therapies are enjoying a moment in the spotlight, as two of the most effective and coveted COVID-19 vaccines, produced by Pfizer/BioNTech and Moderna, employ the technology. Once thought too fragile for therapeutic use, the COVID-19 pandemic has shown that mRNA is a force to be reckoned with, if used correctly. However, the technology does have some drawbacks, especially for routine use in large populations, as it requires storage at very low temperatures, making necessary expensive and impractical cold-chain transport.
The fragility of mRNA molecules also underlies their need for special nano-scale packaging so that they can reach their target cells without being destroyed within the body. At present, this can be achieved using lipid vesicles that cradle the fragile molecules until they are taken up into cells. However, researchers are still learning the best ways to package and deliver mRNA, and optimizing this is key to advancing the technology. At present, mRNA delivery to cells is somewhat inefficient and there is room for improvement.
Finding better ways to efficiently deliver mRNA nearly requires a way to track where the molecule travels. Until now this has been very difficult. This latest technique from Chalmers University of Technology changes that. It involves a fluorescent unit created by the researchers, which can replace a base called cytosine that is normally part of mRNA, resulting in fluorescent mRNA strands. The fluorescently labelled molecules can be viewed through a microscope, allowing researchers to track their movement as they are taken up by cells and then distributed within the cells themselves.
“The great benefit of this method is that we can now easily see where in the cell the delivered mRNA goes, and in which cells the protein is formed, without losing RNA’s natural protein-translating ability,” said Elin Esbjörner, a researcher involved in the study.
The researchers hope that the technique could help accelerate the development of a new wave of mRNA therapeutics. “Since our method can help solve one of the biggest problems for drug discovery and development, we see that this research can facilitate a paradigm shift from traditional drugs to RNA-based therapeutics,” said Marcus Wilhelmsson, another researcher involved in the study.
Study in Journal of the American Chemical Society: Stealth Fluorescence Labeling for Live Microscopy Imaging of mRNA Delivery